Published online 5 November 2001. doi:10.1083/jcb1554rr1
© The Rockefeller University Press,
0021-9525/2001/11/496 $5.00
The Journal of Cell Biology, Volume 155, Number 4, November 12, 2001 496-496
A fatal break up
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Drp1 (green) translocates to, and helps divide, mitochondria (red) during apoptosis (right).
Youle/Elsevier
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Apoptosis can be short-circuited by inhibiting a protein that stimulates mitochondria to split. The finding suggests that mitochondrial fission is indispensable for programmed cell death.Most mitochondria are not the solitary, kidney bean–shaped objects you see in the textbooks, says Richard Youle (National Institute of Neurological Disorders and Stroke, Bethesda, MD). Instead, the organelles have an active social life, often linking up to form long, interconnected chains, and then sometimes splitting apart again. During apoptosis, however, networks of mitochondria shatter into small, "punctiform" blobs. The mitochondria of a dying cell also spill their guts, dumping proteins such as cytochrome c that further drive apoptosis.
To discover what spurs mitochondrial fission, Youle and colleagues focused on a protein called Drp1, a member of a class of proteins known as dynamins that are involved in endocytosis and vesicle formation. In a healthy cell, Drp1 loiters in the cytosol and regulates the division of mitochondria. But the authors found that during apoptosis, Drp1 swarms to the mitochondria, concentrating at the sites where the organelles tend to cleave. Youle believes that these Drp1 complexes hasten mitochondrial breakup. Blocking Drp1 not only slows the splitting of mitochondrial networks, it also prevents release of cytochrome c and thwarts apoptosis. The researchers plan to probe how Drp1 works and why its actions change once apoptosis begins. "It works in healthy cells to regulate mitochondrial dynamics," Youle says, "the question is how does it change from its normal function to its proapoptotic function." 
Reference:
Frank, S., et al. 2001. Dev. Cell. 1:515–525.[Medline]
Mitch Leslie
mleslie{at}cybermesa.com
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