Scheckhuber CQ, et al. (2011) Unopposed mitochondrial fission leads to severe lifespan shortening. Cell Cycle 10(18):3105-10
Abstract: Mitochondrial morphology is controlled by the opposing processes of fusion and fission. Previously, in baker's yeast it was shown that reduced mitochondrial fission leads to a network-like morphology, decreased sensitivity for the induction of apoptosis and a remarkable extension of both replicative and chronological lifespan. However, the effects of reduced mitochondrial fusion on aging are so far unknown and complicated by the fact that deletion of genes encoding components of mitochondrial fusion are often lethal to higher organisms. This is also true for the mammalian OPA1 protein, which is a key regulator of mitochondrial inner membrane fusion. Baker's yeast contains an OPA1 ortholog, Mgm1p. Deletion of Mgm1 is possible in yeast due to the fact that mitochondrial function is not essential for growth on glucose-containing media. In this study, we report that absence of mitochondrial fusion in the ?mgm1 mutant leads to a striking reduction of both replicative and chronological lifespan. Concomitantly, sensitivity to apoptosis elicitation via the reactive oxygen species hydrogen peroxide is substantially increased. These results demonstrate that the unopposed mitochondrial fission as displayed by the ?mgm1 mutant strongly affects organismal aging. Moreover, our results bear important clues for translational research to intervene into age-related degenerative processes also in multicellular organisms including humans.
|Status: Published||Type: Journal Article||PubMed ID: 21912203|
Topics addressed in this paper
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