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  • richardmitnick 10:37 am on November 29, 2017 Permalink | Reply
    Tags: , , Dnm1 proteins, Mitochondria, , , , UCLA bioengineers discover mechanism that regulates cells’ ‘powerhouses’   

    From UCLA Newsroom: “UCLA bioengineers discover mechanism that regulates cells’ ‘powerhouses’” 


    UCLA Newsroom

    November 27, 2017
    Matthew Chin

    1
    In this artist’s rendering, Dnm1 proteins surrounding a mitochondrion are breaking it up into two. Jaime de Anda/ACS Central Science.

    UCLA bioengineers and their colleagues have discovered a new perspective on how cells regulate the sizes of mitochondria, the parts of cells that provide energy, by cutting them into smaller units.

    The researchers wrote that this finding, demonstrated with yeast proteins, could eventually be used to help address human diseases associated with an imbalanced regulation of mitochondria size — for example, Alzheimer’s or Parkinson’s diseases. In addition, since having mitochondria that are too small or too large can potentially lead to incurable diseases, it is conceivable that the proteins responsible for this process could be potential targets for future therapies.

    The study was published in ACS Central Science and was led by UCLA bioengineering professor Gerard Wong.

    Inside the cell, mitochondria resemble the long balloons used to create balloon animals. If the mitochondria are too long, they can get tangled. Their sizes are known to be primarily regulated by two proteins, one of which breaks up longer mitochondria into smaller sizes. They are known as cells’ “powerhouses” as they convert chemical energy from food into a form useful for cells to perform all their functions.

    Keeping mitochondria at optimal sizes is important to cells’ health. An insufficient amount of the regulating protein, known as Dnm1, results in the mitochondria getting too long and tangled. Too much Dnm1 results in too many short mitochondria. In both cases, the mitochondria are rendered essentially ineffective as power providers for the cell. This situation could lead to neurodevelopmental disorders or neurodegenerative diseases, such as Alzheimer’s or Parkinson’s.

    To better understand this mechanism, the researchers used a machine-learning approach they developed in 2016 to figure out exactly how the proteins break up one mitrochondrion into two smaller ones. They also used a powerful technique called “synchrotron small-angle X-ray scattering” at the Stanford Synchrotron Radiation Lightsource, a U.S. Department of Energy research facility, to see how these proteins deform mitochondrial membranes during this process.

    SLAC/SSRL

    Before this study, it was thought that these proteins encircled the mitochondria, then cut it in two by simply squeezing tightly. The process, the team discovered, is more subtle.

    “When Dnm1 wraps around mitochondria, it has been previously shown that the protein physically tightens and pinches,” said Michelle Lee, a recent UCLA bioengineering doctoral graduate who was advised by Wong and is one of two lead authors of the study. “What we found is that when Dnm1 contacts the mitochondrial surface, it also makes that area of the mitochondrion itself more moldable and easier to undergo cleavage. These two effects work hand in hand to make the process of mitochondrial division efficient.”

    The other lead author is Ernest Lee, a graduate student in the UCLA-Caltech Medical Scientist Training Program and a bioengineering graduate student also advised by Wong. He carried out the computational analyses for the experiment.

    “Using our machine-learning tool, we were able to discover hidden membrane-remodeling activity in Dnm1, consistent with our X-ray studies,” Lee said. “Interestingly, by analyzing distant relatives of Dnm1, we found that the protein gradually evolved this ability over time.”

    “This is a very unexpected result — no one thought these molecules would have a split personality, with both personalities necessary for the biological function,” said Wong, who is also a UCLA professor of chemistry and biochemistry and is a member of the California NanoSystems Institute. “The multifunctional behavior we identified may be the rule rather than the exception for proteins.”

    Other authors include Andy Ferguson from the University of Illinois at Urbana-Champaign and Blake Hill from the Medical College of Wisconsin.

    The research was supported by the National Science Foundation and the National Institutes of Health, with additional support from the Department of Energy for imaging experiments.

    See the full article here .

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  • richardmitnick 10:26 am on September 9, 2016 Permalink | Reply
    Tags: , , Mitochondria, ,   

    From SA: “Promising Links Found between Different Causes of Parkinson’s” 

    Scientific American

    Scientific American

    September 8, 2016
    Karen Weintraub

    Glitches in cells’ mitochondria power plants underlie various types of cases.

    1
    Mitochondrion, coloured transmission electron micrograph (TEM). Credit: CNRI Getty Images

    Researchers have long believed that problems with mitochondria—the power plants of cells—underlie some cases of Parkinson’s disease. Now a new study details those problems, and suggests that they may form a common thread linking previously unexplained cases of the disease with those caused by different genetic anomalies or toxins.

    Finding a common mechanism behind different suspected causes of Parkinson’s suggests that there might also be a common means to measure, treat or cure it, says Marco Baptista, research director at the nonprofit Michael J. Fox Foundation, a leading center for study and advocacy in the fight against Parkinson’s.

    The study, published Thursday in Cell Stem Cell, did identify a possible way to reverse the damage of Parkinson’s—but only in individual cells and fruit flies. Finding a treatment that does the same thing in people will be challenging, Baptista says.

    Roughly one million Americans have Parkinson’s disease, which is characterized by motor problems and can cause other symptoms including cognitive and gastrointestinal difficulties. About 1 to 2 percent of cases are linked to mutations in the LRRK2 gene, with far fewer associated with genes known as PINK1 and Parkin. Exposure to environmental factors such as toxic chemicals can also lead to Parkinson’s, although most cases have no obvious cause.

    In the new paper Xinnan Wang, an assistant professor of neurosurgery at Stanford University, and her colleagues show that mitochondria are underpowered in several types of Parkinson’s and that these mitochondria also release toxic chemicals. Looking at fly models of the disease as well as cells taken from patients, the researchers found that they could correct these problems and reverse neurodegeneration if they reduced levels of a protein involved in mitochondrial activity. “I think it’s a really cool piece of work,” says Thomas Schwarz, a professor of neurology and neurobiology at Harvard University who was not involved in the research but was Wang’s postdoctoral adviser.

    It had been clear that Parkinson’s cases caused by toxins, or by Parkin or PINK1 mutations, involved mitochondria problems, Schwarz says. But the new paper shows that Parkinson’s driven by the LRRK2 gene is also subject to the same mechanism and hints that unexplained cases may also involve the same difficulties in clearing faulty mitochondria from cells. “Here’s the best evidence yet that even those forms are some sort of mitochondriopathy,” Schwarz says. “Seeing those completely disparate, unrelated spontaneous cases—linked up to this question of how are mitochondria cleared and how is their movement controlled—is absolutely fascinating.”

    One question that remains is why would a general problem of cellular physiology cause Parkinson’s? Both Schwarz and Wang have hypotheses: Wang says that the brain cells whose degeneration leads to Parkinson’s—the cells that control release of the neurotransmitter dopamine—are particularly energy-dependent and vulnerable to stress. Deprive a skin cell of energy and it won’t work as efficiently; deprive a dopaminergic neuron of energy and it may die, she adds.

    Schwarz says these neurons are also distinctive in their anatomy. They have so many branches linking them to other brain cells that they can extend up to 4.5 meters in length. Mitochondria are distributed along these branches and must continually be refreshed, with old ones cleared out on the order of some 33,000 mitochondria per cell each day. “That’s just a staggering burden for the cell to carry,” says Schwarz, who in his own research explores how mitochondria move along these axons. “That’s why even a minor slowing or defect in the way the mitochondria are cleared out, or damaged proteins are dealt with, winds up being a major crisis for a cell that has 4.5 meters of axon, compared to a liver cell or even your average neuron elsewhere in the brain.” Figuring out a way to measure this overload before it brings about symptoms of Parkinson’s might lead to earlier diagnoses, before irrevocable damage is done, he adds.

    The paper released Thursday addresses the mystery of how Parkinson’s caused by PINK1 and Parkin mutations, which are known to affect mitochondria, could share the same symptoms as those caused by mutations in the LRRK2 gene, which is involved in how cells take out their trash. Wang and her team found that problems turn up when spent mitochondria are not cleared properly from the cell, a situation that provides a link between the two problems. The different mutations may act on the mitochondria differently but both end up causing the same mitochondrial dysfunction, Wang says. These dysfunctional mitochondria also produce toxins, much like a power plant does, she says, further damaging the cells.

    Asa Abeliovich, a pathologist and neurologist at Columbia University who was not part of this study, says the paper effectively links these two genetic routes to Parkinson’s: the garbage disposal problem and the toxic accumulation that occurs when cellular energy plants go awry. Abeliovich, however, thinks it is still speculative to conclude these problems are also to blame for the noninherited cases of Parkinson’s.

    Wang agrees that she needs to test her theories in other models of Parkinson’s before declaring that a cure might lie in fixing mitochondrial problems. Just because the team found the mitochondrial problems in human cells and in a fly model of Parkinson’s “doesn’t necessarily mean that in humans it is the cause [of Parkinson’s],” Wang says, “but suggests it is a possibility—[and] suggests a future direction to look in human patients and see if lowering this protein has any therapeutic benefits.”

    See the full article here .

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  • richardmitnick 2:26 pm on May 13, 2016 Permalink | Reply
    Tags: , , , Look, Ma! No Mitochondria, Mitochondria,   

    From NPR: “Look, Ma! No Mitochondria” 

    NPR

    National Public Radio (NPR)

    May 12, 2016
    Nell Greenfield Boyce
    1
    These mitochondria, in red, are from the heart muscle cell of a rat. Mitochondria have been described as “the powerhouses of the cell” because they generate most of a cell’s supply of chemical energy. But at least one type of complex cell doesn’t need ’em, it turns out.
    Science Source

    Scientists have found a microbe that does something textbooks say is impossible: It’s a complex cell that survives without mitochondria.

    Mitochondria are the powerhouses inside eukaryotic cells, the type of complicated cell that makes up people, other critters and plants and fungi. All eukaryotic cells contain a nucleus and little organelles — and one of the most famous was the mitochondrion.

    “They were considered to be absolutely indispensable components of the eukaryotic cell and the hallmark of the eukaryotic cell,” says Anna Karnkowska, a researcher in evolutionary biology at the University of British Columbia in Vancouver. Karnkowska and her colleagues describe their new find in a study published* online Thursday in the journal Current Biology.

    1
    This is a light micrograph of the microbe that evolutionary biologists say lives just fine without any mitochondria.
    Naoji Yubuki/Current Biology

    Mitochondria have their own DNA, and scientists believe they were once free-living bacteria that got engulfed by primitive, ancient cells that were evolving to become the complex life forms we know and love today.

    For decades, researchers have tried to find eukaryotic cells that don’t have mitochondria — and for a while they thought they’d found some. One example is Giardia, a human gut parasite that causes diarrhea. It was considered to be a kind of living fossil because it had a nucleus but didn’t seem to have acquired mitochondria. But additional studies on Giardia and other microbes showed that actually, the mitochondria were there.

    “It turned out that all of them actually had some kind of remnant mitochondrion,” says Karnkowska, who notes that mitochondria perform key jobs in the cell beyond just generating power.

    A biggie is assembling iron-sulfur clusters for certain proteins, which is thought to be a mitochondrial function that’s really essential. So even if a microbe powers itself in a different way and has a limited form of the organelle that isn’t the same as the mitochondria found in people, Karnkowska says, “it’s still a mitochondrion and it has some important function for the cell.”

    That kind of vestigial mitochondrion is what she expected to find when she was a researcher at Charles University in Prague and started investigating a particular gut microbe that had been isolated from a researcher’s pet chinchilla.

    After she and her colleagues sequenced the gut microbe’s genome, however, they found no trace that it made any mitochondrial proteins at all. “So that’s a great surprise for us,” she says. “That should theoretically kill the cell — it shouldn’t exist.”

    What they learned is that instead of relying on mitochondria to assemble iron-sulfur clusters, these cells use a different kind of machinery. And it looks like they acquired it from bacteria.

    The researchers say this is the first example of any eukaryote that completely lacks mitochondria.

    Michael Gray, a biochemist at Dalhousie University in Halifax, Nova Scotia, says the researchers have made a “compelling” case that they have a bona fide eukaryote without any vestige of a mitochondrion; he calls the finding “unprecedented.”

    “The observation is significant, in that it clearly demonstrates that a eukaryote can still be a eukaryote without having a mitochondrion,” he tells Shots via email.

    However, the results do not negate the idea that the acquisition of a mitochondrion was an important and perhaps defining event in the evolution of eukaryotic cells, he adds.

    That’s because it seems clear that this organism’s ancestors had mitochondria that were then lost after the cells acquired their non-mitochondrial system for making iron-sulfur clusters.

    “This is not the missing link of eukaryotic evolution,” agrees Mark Van Der Giezen, a researcher in evolutionary biochemistry at the University of Exeter in the United Kingdom.

    Still, he says, it is an example of how flexible life is.

    “It lives in an area without oxygen and therefore can get rid of a lot of biochemistry that you and I would need in our cells to survive,” says Van Der Giezen. “This organism managed to adapt in such a way that it could lose an organelle, which every textbook will tell you is an essential feature of eukaryotes. That’s pretty amazing. It shows you that life is extremely creative in finding a way to eke out an existence.”

    *Science paper:
    A Eukaryote without a Mitochondrial Organelle

    See the full article here.

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  • richardmitnick 3:59 pm on January 21, 2016 Permalink | Reply
    Tags: , Mitochondria, , Salk scientists discover how mitochondria recover after damage   

    From Salk: “How the cell’s power station survives attacks” 

    Salk Institute bloc

    Salk Institute for Biological Studies

    January 14, 2016
    No writer credit found

    Salk scientists discover how mitochondria recover after damage, offering clues to cancer, diabetes and brain disease

    Mitochondria, the power generators in our cells, are essential for life. When they are under attack—from poisons, environmental stress or genetic mutations—cells wrench these power stations apart, strip out the damaged pieces and reassemble them into usable mitochondria.

    Now, scientists at the Salk Institute have uncovered an unexpected way in which cells trigger this critical response to threats, offering insight into disorders such as mitochondrial disease, cancer, diabetes and neurodegenerative disease—particularly Parkinson’s disease, which is linked to dysfunctional mitochondria. The work appears January 15, 2016 in Science.

    “Outside marauders come into these power stations of the cell—the mitochondria—and in response, the power stations break into smaller fragments,” says Reuben Shaw, senior author and Salk professor in the Molecular and Cell Biology Laboratory.

    In an average human cell, anywhere from 100 to 500 mitochondria churn out energy in the form of ATP molecules, which act like batteries to carry power to the rest of the cell. At any given time, one or two mitochondria fragment (fission) or reform (fusion) to cycle out any damaged parts. But when a poison—like cyanide or arsenic—or other dangers threaten the mitochondria, a mass fragmentation takes place.

    Researchers have known for years that mitochondria undergo this fragmentation when treated with drugs that affect the mitochondria, but the biochemical details of how the mitochondria damage is sensed and how that triggers the rapid fission response has not been clear until now.

    In the new work, the Salk team found that when cells are exposed to mitochondria damage, a central cellular fuel gauge, the enzyme AMPK, sends an emergency alert to mitochondria instructing them to break apart into many tiny mitochondrial fragments. Interestingly, AMPK is activated by the widely used diabetes therapeutic metformin, as well as exercise and a restricted diet. The new findings suggest that some of the benefits from these therapies may result from their effects in promoting mitochondrial health.

    Temp 1
    Scientists at the Salk Institute (from left: Reuben Shaw, Sebastien Herzig and Erin Toyama) have uncovered an unexpected way in which cells trigger a critical response to mitochondrial threats, offering insight into disorders such as mitochondrial disease, cancer, diabetes and neurodegenerative disease—particularly Parkinson’s disease, which is linked to dysfunctional mitochondria. Credit: Salk Institute

    Prior research by Shaw’s group and others had uncovered AMPK’s role in helping to recycle damaged mitochondrial pieces as well as signaling to the cell to make new mitochondria. But this new role of rapidly triggering mitochondrial fragmentation “really places AMPK at the heart of mitochondria health and long-term well-being,” says Shaw, who is also holder of the William R. Brody Chair.

    To uncover exactly what happens in those first few minutes, the team used the gene editing technique CRISPR to delete AMPK in cells and showed that, even when poison or other threats are introduced to the mitochondria, they do not fragment without AMPK. This indicates that AMPK somehow directly acts on mitochondria to induce fragmentation.

    The group then looked at a way to chemically turn on AMPK without sending attacks to mitochondria. To their surprise, they found that activating AMPK alone was enough to cause the mitochondria to fragment, even without the damage.

    “I could not believe how black and white the results were. Just turning on AMPK by itself gives you as much fragmentation as a mitochondrial poison,” says Shaw.

    The team discovered why this was: when the cell’s power stations are disrupted, the amount of energy floating around a cell—ATP—is lowered. After just a few minutes, AMPK detects this reduction of energy in the cell and hurries to the mitochondria. Like a guard pulling a fire alarm, AMPK activates a receptor on the outside membrane of a mitochondrion to signal it to fragment.

    Drilling down further, the researchers found that AMPK actually acts on two areas of a mitochondrial receptor, called mitochondrial fission factor (MFF), to start the process. MFF calls over a protein, Drp1, that binds and wraps around the mitochondrion like a beaded noose to twist and break it apart.


    Watch mp4 video here .

    “We discovered that the modification of MFF by AMPK is needed for MFF to call over more Drp1 to the mitochondria,” says Erin Quan Toyama, one of the first authors of the paper and a Salk research associate. “Without AMPK sending the alarm, MFF cannot call over to Drp1 and there is no new fragmentation of mitochondria after damage.”

    In the future, the team is interested in addressing what other consequences this signaling pathway has for specific cell types, according to Sébastien Herzig, the other first author of the paper and a Salk research associate. “We want to see what a defect in communication between the mitochondria and AMPK would do to different tissues, particularly ones very dependent on healthy mitochondria, such as brain, muscle and heart,” says Herzig.

    Temp 2
    Scientists at the Salk Institute demonstrated how a molecular sensor detects damage in mitochondria (green) and induces reorganization of the entire mitochondrial network (nuclei in blue). Normal mitochondria (left) undergo massive reorganization (right) after exposure to the toxin rotenone. Credit: Salk Institute

    Adds Toyama, “On one hand, AMPK is known to be important for type 2 diabetes, immune disease and cancer. On the other hand, mitochondrial dysfunction is becoming increasing connected to metabolic diseases and neurodegenerative diseases. We’re making some of the first steps in connecting these two things that have major disease implications.”

    Other authors of the work were Kristina Hellberg and Nathan P. Young of the Salk Institute; Julien Courchet, Tommy L. Lewis Jr. and Franck Polleux of Columbia University; and Oliver C. Losón, Hsiuchen Chen and David C. Chan of the California Institute of Technology.

    The work was funded in part by the Howard Hughes Medical Institute, NIH and The Leona M. and Harry B. Helmsley Charitable Trust.

    PUBLICATION INFORMATION

    JOURNAL

    Science

    TITLE

    AMP-activated Protein Kinase mediates mitochondrial fission in response to energy stress

    AUTHORS

    Erin Quan Toyama, Sébastien Herzig, Julien Courchet, Tommy L. Lewis Jr., Oliver C. Losón, Kristina Hellberg, Nathan P. Young, Hsiuchen Chen, Franck Polleux, David C. Chan, Reuben J. Shaw

    See the full article here .

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    Every cure has a starting point. Like Dr. Jonas Salk when he conquered polio, Salk scientists are dedicated to innovative biological research. Exploring the molecular basis of diseases makes curing them more likely. In an outstanding and unique environment we gather the foremost scientific minds in the world and give them the freedom to work collaboratively and think creatively. For over 50 years this wide-ranging scientific inquiry has yielded life-changing discoveries impacting human health. We are home to Nobel Laureates and members of the National Academy of Sciences who train and mentor the next generation of international scientists. We lead biological research. We prize discovery. Salk is where cures begin.

     
  • richardmitnick 8:48 pm on December 11, 2014 Permalink | Reply
    Tags: , , Mitochondria,   

    From Wisconsin: “New studies power legacy of UW-Madison mitochondrial research “ 

    U Wisconsin

    University of Wisconsin

    Dec. 11, 2014
    Kelly April Tyrrell

    It was the yellow color of the solution, pulled from cauliflower, that set Frederick Crane’s hallmark achievement into its final motion.

    Crane was a researcher under David E. Green in the early days of the University of Wisconsin-Madison Enzyme Institute, in a lab group on a mission to determine, bit by bit, how mitochondria — the power plants of cells — generate the energy required to sustain life.

    s
    An assortment of biochemical approaches, both modern and classic, is pictured with a 3-D model of the COQ9 protein structure used by UW-Madison researchers. The university’s mitochondrial research dates back nearly 60 years. Photo: Matthew Stefely/Pagliarini Lab

    m
    Mitochondrion ultrastructure. A mitochondrion has a double membrane; the inner one contains its chemiosmotic apparatus and has deep grooves which increase its surface area. While commonly depicted as an “orange sausage with a blob inside of it” (like it is here), mitochondria can take many shapes[17] and their intermembrane space is quite thin.

    In the early 1950s, the lab was looking for the missing piece that connected each of the individual parts of the mitochondrial energy machine — the electron transport chain — like the gears needed to operate an engine.

    What Crane found, a compound called coenzyme Q, was to become a major part of the legacy of mitochondrial research at UW-Madison, but it was no accident. It was “the result of a long train of investigation into a mechanism of, and compounds involved in, biological energy conversion,” Crane wrote in a 2007 review article of his discovery.

    c
    coenzyme Q

    dp
    Photo: Dave Pagliarini

    Almost six decades later, that “long train” has grown even longer. Dave Pagliarini, a UW-Madison assistant professor of biochemistry, has established a new laboratory studying these dynamic organelles, the mitochondria. He recently published two studies shedding more light on coenzyme Q and how it’s made, one in the Proceedings of the National Academy of Science (PNAS) in October and another today in Molecular Cell.

    “Mitochondria are tiny structures in nearly all of our cells that are essential for producing our cellular energy and that house a wide array of metabolic processes,” Pagliarini says. “When mitochondria don’t work properly, many different human diseases can arise.”

    These include cerebellar ataxia, certain kidney diseases and severe childhood-onset multisystemic disease. Coenzyme Q deficiency is a hallmark of these diseases, but scientists aren’t sure why.

    “Nearly 60 years later, there is still much we don’t know about how mitochondria make coenzyme Q and that has complicated our ability to target this pathway therapeutically,” Pagliarini says.

    The new studies, he says, are about two proteins known to be important in the coenzyme Q production pathway. Mutations in them lead to human disease. But before now, no one knew a thing about their biochemical functions.

    One of these proteins is COQ9, and graduate student Danielle Lohman, co-lead author of the PNAS study, explains it’s somehow involved in making coenzyme Q in mitochondria. The other lead author is Farhad Forouhar at Columbia University.

    The study team — which includes researchers from UW-Madison and other universities in the U.S. and Spain — found COQ9 is essential for coenzyme Q production in mice. To study what it looks like, they created crystals of COQ9 in the lab and found it binds fatty substances like those Crane first observed in his studies, like coenzyme Q.

    With these mitochondrial proteins and many others, much is still unknown. They represent an untapped resource, Pagliarini says, but the mining for answers is happening right here, where coenzyme Q was first found.

    In his day, while others were looking for proteins to be the missing part of the mitochondrial energy chain, Crane was looking for fatty, vitamin-like compounds. His hunch turned out to be correct.

    Today, Pagliarini and Lohman have a hunch, too, that COQ9 may be grabbing hold of an immature form of coenzyme Q and helping it develop. The prevailing notion in the mitochondrial field is that coenzyme Q is made through the actions of a collaborative complex of proteins, of which CoQ9 may be a part.

    Only time and future study will tell, but lending credence to the idea is the research team’s additional finding that COQ9 cooperates with another protein called COQ7.

    “We went from not knowing why this protein would be needed to make coenzyme Q, to having a model for what it might be doing,” Lohman says.

    Two other graduate students in Pagliarini’s lab, Jonathan Stefely and Andrew Reidenbach, worked together to lead the Molecular Cell study of a human mitochondrial protein also involved in building coenzyme Q, called ADCK3.

    “Like COQ9, there are patients with mutations in ADCK3 who have really bad cerebellar ataxia, described in the medical literature not too long ago,” says Stefely.

    Also like COQ9, ADCK3’s biochemical function was previously unknown. The research team — from UW-Madison, the University of Georgia and the University of San Diego — similarly created a crystal of the protein and determined the protein family it’s related to: the kinase superfamily. Craig Bingman, a research scientist at UW-Madison, performed the challenging crystal work.

    While solving the crystal structure revealed the protein’s genealogy, the findings also provided the researchers with information that could have implications for cancer and other cellular processes that may rely on the actions of this protein and its close relatives. It provides a platform for further discovery.

    “It has some very specific and unique features that separate it from the rest of this kinase superfamily,” says Reidenbach.

    “We were also able to show the first enzymatic activity for ADCK3, which was a major milestone in this field,” Stefely adds.

    For Pagliarini and his students — the future of UW-Madison mitochondrial research — the old, yet still-wide-open field of study offers plenty of opportunity for curiosity, and promise.

    With these mitochondrial proteins and many others, much is still unknown. They represent an untapped resource, Pagliarini says, but the mining for answers is happening right here, where coenzyme Q was first found.

    In his lab, Pagliarini is on a quest to describe the hundreds of mitochondrial proteins with functions yet unknown. With colleagues, he has amassed a collection of them in an inventory they’ve called the MitoCarta.

    “I stumbled into mitochondrial biology early in my graduate career and spent my postdoctoral years systematically identifying new mitochondrial proteins” says Pagliarini. “Now, I am very interested in annotating the functions of these ‘orphan’ proteins.”

    It’s this same natural curiosity that fueled Crane and eventually led to his discovery of coenzyme Q. As part of Green’s group, he was also systematically separating the parts of the mitochondrial energy machinery, asking questions along the way.

    He was using beef hearts — which he got from the Oscar Mayer plant in Madison — to isolate mitochondria, and they came out in a brown solution. But Crane was originally trained as a plant physiologist and in his spare time, he started isolating mitochondria from cauliflower, too. They came out in a yellow solution, which told him to keep looking for fatty, vitamin-A-like molecules, leading him ultimately to coenzyme Q.

    The give-away color was simply masked by the brown-colored elements of the beef.

    For Pagliarini and his students — the future of UW-Madison mitochondrial research — the old, yet still-wide-open field of study offers plenty of opportunity for curiosity, and promise.

    “It gives you a sense of wonder; for me, like all scientists, I just want to know how things work,” says Lohman. “This seemed like fruit ripe for the picking.”

    See the full article here.

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    In achievement and prestige, the University of Wisconsin–Madison has long been recognized as one of America’s great universities. A public, land-grant institution, UW–Madison offers a complete spectrum of liberal arts studies, professional programs and student activities. Spanning 936 acres along the southern shore of Lake Mendota, the campus is located in the city of Madison.

     
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