Unopposed mitochondrial fission leads to severe lifespan shortening

• Published in: Cell cycle (Georgetown, Tex.) Tex.), 2011-09, Vol.10 (18), p.3105-3110
• Main Authors: Scheckhuber, Christian Q., Wanger, Ruth A., Mignat, Cora A., Osiewacz, Heinz D.
• Format: Article
• Language: English
• Subjects: Binding; Biology; Bioscience; Calcium; Cancer; Cell; Culture Media - chemistry; Cycle; Gene Deletion; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Hydrogen Peroxide - metabolism; Hydrogen Peroxide - pharmacology; Landes; Membrane Fusion; Microbial Sensitivity Tests; Microscopy, Fluorescence; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial Membranes - metabolism; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Organogenesis; Phenotype; Plasmids - genetics; Plasmids - metabolism; Proteins; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Time Factors; Transformation, Genetic
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.10.18.17196

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 Δmgm1 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 Δmgm1 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.