PerspectiveCell Biology

Mitochondrial Dynamics and Apoptosis—the ER Connection

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Science  31 Aug 2012:
Vol. 337, Issue 6098, pp. 1052-1054
DOI: 10.1126/science.1224709

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Mitochondria are endosymbiotic organelles that were pivotal in the evolution of eukaryotic multicellular organisms, enabling cells, through production of adenosine 5′-triphosphate, to overcome a steep energetic barrier (1). Another essential feature of multicellularity is programmed cell death or apoptosis—a process in which mitochondria also play a critical role. During intrinsic apoptosis, a signaling platform assembles on mitochondria that in some organisms is harnessed to permeabilize the outer mitochondrial membrane and release proapoptotic proteins. Assembly of this platform is accompanied by dramatic changes in the dynamic behavior of mitochondria, which influence cell death. The dynamic properties of mitochondria are dependent on their division and fusion and govern the overall shape, connectedness, and distribution of mitochondria in cells. On page 1062 in this issue, Youle and van der Bliek (2) review the interplay between mitochondrial dynamics and mitochondrial quality-control and stress pathways. Here, we speculate on the role of mitochondrial division and fusion in the ultimate stress response, cell death. The recent discovery that the endoplasmic reticulum (ER), another ancient endomembrane organelle, actively participates in mitochondrial division has led to a new model linking mitochondrial dynamics and cell death. This suggests an unexpected convergence during evolution of mitochondria and ER—the two dominant endomembrane systems in eukaryotic cells that have previously been viewed as functionally distinct.