January 8, 2015

If you are lucky in life, there is at least one person who will always be there for you—a parent, your spouse, maybe even your pooch. As we understand more and more of what goes on inside a cell, it has become clear that actin is always there for the cell’s many organelles. Actin is so supportive and encouraging, and without it our cells would just be puddles of fats and proteins. Today’s images are from a paper describing the role of actin in mitochondrial fission. 

Mitochondria are dynamic organelles that divide by fission. Although a role for the actin cytoskeleton in mitochondrial fission has been suggested, the exact mechanism is unclear. Recent work by Li and colleagues shows a transient association of F-actin (filamentous actin) to mitochondria at the start of fission. Downregulation of the actin regulators cortactin, cofilin, and Arp2/3 caused elongation of mitochondria. Li and colleagues tested the role of Drp1, which is a key player in mitochondrial division, on F-actin assembly during fission. Drp1 inhibition prolonged the localization of F-actin and several actin regulators at mitochondria during fission. In the left group of images above, F-actin (green) and mitochondria (red) are visible in a control mammalian cell (bottom row is at higher magnification). The group of images on the right shows mammalian cells after chemical induction of mitochondrial fission: 2 minutes after drug treatment, many F-actin-rich mitochondria are visible.

Li, S., Xu, S., Roelofs, B., Boyman, L., Lederer, W., Sesaki, H., & Karbowski, M. (2014). Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission The Journal of Cell Biology, 208 (1), 109-123 DOI: 10.1083/jcb.201404050

October 28, 2014

If you’ve ever tried to get your kids to share a donut, you understand the importance to dividing things equally (and learning crucial lessons…just buy more donuts next time...I mean, seriously!). Cell division is no different—chromosomes and organelles must all get divided equally. Today’s images are from a paper showing how mitochondria are positioned during cell division in order to allow equal segregation.

Many years of research have focused on the equal segregation of chromosomes during cell division. Organelles such as mitochondria must also be segregated equally in a dividing cell, and errors in this process can lead to disease. A recent paper identifies the actin motor Myosin-XIX (Myo19) as a key player in mitochondrial partitioning during cell division. Myo19 is localized to mitochondria, and cells depleted of Myo19 have an abnormal distribution of mitochondria. Rohn and colleagues found that cells lacking Myo19 experience stochastic division failure, suggesting that mitochondria are physically preventing successful cell division. The images above show dividing cells labeled to visualize mitochondria (green) and the mitotic spindle (red) in control cells (top two rows) and cells depleted of Myo19 (bottom two rows). Without Myo19, mitochondria moved towards spindle poles at the onset of anaphase, causing an asymmetric distribution at division when compared with control cells.

BONUS!! Here is a rotating 3D reconstruction of an A549 stained to visualize microtubules (green), mitochondria (red), and DNA (blue). Omar Quintero, HighMag friend and a co-author from today’s paper, loves this image: “I like it because it reminds me of the scenes in StarWars where the Rebels are planning their attack on the Death Star.”

Rohn, J., Patel, J., Neumann, B., Bulkescher, J., Mchedlishvili, N., McMullan, R., Quintero, O., Ellenberg, J., & Baum, B. (2014). Myo19 Ensures Symmetric Partitioning of Mitochondria and Coupling of Mitochondrial Segregation to Cell Division Current Biology DOI: 10.1016/j.cub.2014.09.045

Copyright ©2014 Elsevier Ltd. All rights reserved.

July 18, 2014

Poor polar bodies typically go the way of that old container of Chinese take-out in your fridge and are eventually dumped. Thanks to a very clever study published in Cell, polar body transfer can prevent the transmission of inherited mitochondrial diseases. Waste not, want not.

The meiotic divisions of an oocyte result in the production of an egg in the extrusion of two very small polar bodies. These polar bodies have the same genetic material as the egg but have only a small number of organelles, including mitochondria. The DNA of mitochondria (mtDNA) can carry mutations that cause a variety of diseases. As mtDNA is maternally inherited due to the abundance of mitochondria in the oocyte, recent studies have focused on the replacement of mutant mtDNA with normal mitochondria to treat these inherited diseases. A recent paper tests the use of polar bodies as the source of donor genomes in a potential new method for mitochondrial replacement. As polar bodies have the same genome as the egg, but does not have mtDNA variants, they can successfully replace the genome in a recipient egg that already has normal mtDNA. Wang and colleagues have shown that polar body genome transfer successfully does just this, and provides a potential new therapy for preventing inherited mitochondrial diseases. The images above show the presence of mitochondria (red) in oocytes and polar bodies. Both polar bodies (PB1 and PB2) have far fewer mitochondria than the ooctyes.

Wang, T., Sha, H., Ji, D., Zhang, H., Chen, D., Cao, Y., & Zhu, J. (2014). Polar Body Genome Transfer for Preventing the Transmission of Inherited Mitochondrial Diseases Cell, 157 (7), 1591-1604 DOI: 10.1016/j.cell.2014.04.042
Copyright ©2014 Elsevier Ltd. All rights reserved.

March 5, 2014

Mitochondria are the cellular power plants, but bigger power plants are not always a good thing. Defects in the regulation of mitochondrial size and dynamics can cause neurodegenerative diseases such as Alzheimer’s disease. Today’s image is from a paper describing an important player in mitochondrial division, or fission.

Mitochondria serve as the cellular power plants due to their production of ATP, the cell’s energy source, and are quite dynamic, with fusion and fission events occurring regularly. Mitochondrial fission is how mitochondria divide, but fission also plays an important role in apoptosis and ridding the cell of damaged mitochondrial components. In current models of fission, the GTPase dynamin (Drp1) forms a ring around and constricts the mitochondrial membranes. A recent paper describes the importance of the myosin II, an actin motor, in Drp1-mediated fission. Korobova and colleagues found that inhibition of myosin II resulted in abnormally long mitochondria. This inhibition of myosin II also affected the presence of Drp1 at mitochondria. In the images above, the use of blebbistatin, a myosin II chemical inhibitor, resulted in long mitochondria (right), compared to control mitochondria (left).

Korobova, F., Gauvin, T., & Higgs, H. (2014). A Role for Myosin II in Mammalian Mitochondrial Fission Current Biology, 24 (4), 409-414 DOI: 10.1016/j.cub.2013.12.032
Copyright ©2014 Elsevier Ltd. All rights reserved.

June 4, 2012

If you’re like me, you look forward to summer’s juicy blueberries. You’ll sprinkle or mix them into everything you eat, and sneak a big handful every time you open your fridge. You tell yourself that it’s all for the antioxidants. Just make a bigger rationalization leap and say you’re helping blueberries fight alongside dividing mitochondria to protect us from the evils of oxidative damage.

Mitochondria are the cell’s main source of energy, and without their dynamic dividing and fusing a cell can suffer. Neurological diseases such as Alzheimer’s, Parkinson’s, and Huntington’s are all associated with defects in mitochondrial division and fusion. A recent paper describes how mitochondrial division helps to protect neurons from oxidative damage, and in turn protects them from neurodegeneration. Kageyama and colleagues looked at postmitotic neurons in mice lacking Drp1, a protein that mediates mitochondrial division. In these neurons lacking Drp1, mitochondria extended into large tubules because of excess fusion, and showed an accumulation of oxidative damage and eventual neurodegeneration. This cell death could be reversed after application of antioxidants. The images above show Purkinje neurons in brain sections from 1, 3, and 6 month old mice (boxed areas show magnified images). Compared with control brain sections (top), Purkinje neurons lacking Drp1 (bottom) experienced dramatic neurodegeneration (90% of cells lost by 6 months).

Kageyama, Y., Zhang, Z., Roda, R., Fukaya, M., Wakabayashi, J., Wakabayashi, N., Kensler, T., Reddy, P., Iijima, M., & Sesaki, H. (2012). Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage originally published in the Journal of Cell Biology, 197 (4), 535-551 DOI: 10.1083/jcb.201110034

October 27, 2011

Apoptosis sounds like a brutal death for a cell—all of that blebbing, fragmentation, and destruction just gives me the willies. Most of the time, cells only go through apoptosis when absolutely necessary thanks to proteins such as Bcl-x_L. A recent paper finds a new, non-apoptosis role for Bcl-x_L in cell health and survival.

The Bcl-2 family is made up of proteins that can either drive or inhibit apoptosis, which is programmed cell death. Bcl-x_L is a Bcl-2 family member that inhibits apoptosis by binding Bax, a pro-apoptosis family member, at the outer membrane of mitochondria. There, Bcl-x_L inhibits the release of cytochrome c, which during apoptosis serves to kick-start a cascade that destroys the cell. A recent paper finds an exciting new role for Bcl-x_L outside of apoptosis. Chen and colleagues found Bcl-x_L localized to the inner mitochondrial membrane, contrary to previous opinion that it is only found at the outer mitochondrial membrane. At the inner membrane, Bcl-x_L is important in maintaining the efficiency of the mitochondria by inhibiting excessive flux of ions across the inner membrane. The images above are electron micrographs of mitochondria. Antibodies that label Bcl-x_L are bound to tiny gold beads, which are found at the inner membrane (black arrows), as well as the outer membrane (arrowheads) and adjacent membranes (line arrows).

Chen, Y., Aon, M., Hsu, Y., Soane, L., Teng, X., McCaffery, J., Cheng, W., Qi, B., Li, H., Alavian, K., Dayhoff-Brannigan, M., Zou, S., Pineda, F., O'Rourke, B., Ko, Y., Pedersen, P., Kaczmarek, L., Jonas, E., & Hardwick, J. (2011). Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential originally published in The Journal of Cell Biology, 195 (2), 263-276 DOI: 10.1083/jcb.201108059

July 21, 2011

When I think of mitochondria, I’m faced with a minor bout of nausea when I remember struggling to memorize all of the steps to oxidative phosphorylation during college. Although my college memories of Napster and the Y2K problem are clearer than those of the citric acid cycle, I know how important mitochondria are. A recent paper describes how mitochondria are anchored throughout the cell.

Mitochondria are organelles that provide metabolic energy to the cell. Depending on the energy needs in different regions of the cell, mitochondria move around using actin- and microtubule-based motors and then anchor themselves in place. A recent paper describes how intermediate filaments bind mitochondria to regulate their distribution and anchor them within the cell. Intermediate filaments provide mechanical strength in many cell types by forming rope-like networks of filaments, and are frequently made of a protein called vimentin. Nekrasova and colleagues found that in cells lacking vimentin, mitochondria were highly mobile within the cell. Images above show the colocalization of mitochondria (purple) and vimentin intermediate filaments (green) in mammalian cells. Middle and right images are higher magnification frames of the boxed regions.

Nekrasova, O., Mendez, M., Chernoivanenko, I., Tyurin-Kuzmin, P., Kuczmarski, E., Gelfand, V., Goldman, R., & Minin, A. (2011). Vimentin intermediate filaments modulate the motility of mitochondria Molecular Biology of the Cell, 22 (13), 2282-2289 DOI: 10.1091/mbc.E10-09-0766

June 9, 2011

There are a lot of great horror movies around, but not a single one features GIANT MITOCHONDRIA! I’m going to call Hollywood directly and suggest a movie about giant mitochondria. Or, I could suggest you check out today’s image and fascinating paper on giant mitochondria in fruit fly sperm.

Sperm can grow quite long in the testes of male fruit flies, with some reaching 6 cm long. These elongated sperm have better success at fertilizing female fruit flies than shorter sperm. A recent paper looks at the cellular mechanisms that allow developing spermatids to grow to such great lengths, and the authors find that giant mitochondria play a very important role. Noguchi and colleagues found that growing mitochondria provide a platform for microtubules to grow in the elongating spermatids, and this combined structure serves as a template for cell shape. Image above shows microtubules (green) and mitochondria (red) in a fruit fly spermatid.

Tatsuhiko Noguchi, Michiko Koizumi, & Shigeo Hayashi (2011). Sustained Elongation of Sperm Tail Promoted by Local Remodeling of Giant Mitochondria in Drosophila Current Biology, 21 (10), 805-814 : doi:10.1016/j.cub.2011.04.016
Copyright ©2011 Elsevier Ltd. All rights reserved.

October 11, 2010

Starting in our high school biology classes, we all learned that mitochondria are the “powerhouses” of the cell. However, how many of us knew mitochondria could play a role in diverse processes ranging from hormone secretion to cell differentiation?

Calcium is a major regulator and signal in countless cellular processes. Mitochondria participate by taking in and storing calcium, which helps buffer the amount of free calcium in the cell. A group recently became the first to identify one of the proteins important for mitochondrial calcium uptake. Images above show this protein, called MICU1 (green), localizing onto mitochondria (red); the merged image (right) shows yellow where the two signals are colocalized.

Reference: Fabiana Perocchi, Vishal M. Gohil, Hany S. Girgis, X. Robert Bao, Janet E. McCombs, Amy E. Palmer, and Vamsi K. Mootha. Adapted by permission from Macmillan Publishers Ltd: Nature 467: 291-296, copyright 2010. Paper can be found here.

March 8, 2010

Mutations in the genes PINK1 and Parkin lead to a form of Parkinsons disease. Both PINK1 and Parkin function in protecting cells from damaged mitochondria, and a recent study helps clear up how. PINK1 accumulates on damaged mitochondria, which in turn recruits Parkin to trigger their elimination. Image shows Parkin (left) can be recruited to distressed and depolarized mitochondria (middle) in the presence of PINK1. Box on right shows an enlarged overlay of Parkin and miotchondria.

Reference: Derek P. Narendra, Seok Min Jin, Atsushi Tanaka, Der-Fen Suen, Clement A. Gautier, Jie Shen, Mark R. Cookson, Richard J. Youle. Authors’ PLoS Biology paper can be found here.

March 1, 2010

Myosin is an actin-based molecular motor that functions in many cellular processes. A novel myosin (Myo19) is associated with mitochondrial, and functions in the movement and dynamics of the mitochondrial network. The image shows a cultured cell with this novel myosin (yellow), actin (purple), and DNA (white).

Reference: Quintero OA, DiVito MM, Adikes RC, Kortan MB, Case LB, Lier AJ, Panaretos NS, Slater SQ, Rengarajan M, Feliu M, Cheney RE

Paper and similar images found in the authors’ Current Biology paper here.