Inhibition of peroxisome fission, but not mitochondrial fission, increases yeast chronological lifespan
نویسندگان
چکیده
Mitochondria are key players in aging and cell death. It has been suggested that mitochondrial fragmentation, mediated by the Dnm1/Fis1 organelle fission machinery, stimulates aging and cell death. This was based on the observation that Saccharomyces cerevisiae Δdnm1 and Δfis1 mutants show an enhanced lifespan and increased resistance to cell death inducers. However, the Dnm1/Fis1 fission machinery is also required for peroxisome division. Here we analyzed the significance of peroxisome fission in yeast chronological lifespan, using yeast strains in which fission of mitochondria was selectively blocked. Our data indicate that the lifespan extension caused by deletion of FIS1 is mainly due to a defect in peroxisome fission and not caused by a block in mitochondrial fragmentation. These observations are underlined by our observation that deletion of FIS1 does not lead to lifespan extension in yeast peroxisome deficient mutant cells.
منابع مشابه
TORC1 signaling inhibition by rapamycin and caffeine affect lifespan, global gene expression, and cell proliferation of fission yeast
Target of rapamycin complex 1 (TORC1) is implicated in growth control and aging from yeast to humans. Fission yeast is emerging as a popular model organism to study TOR signaling, although rapamycin has been thought to not affect cell growth in this organism. Here, we analyzed the effects of rapamycin and caffeine, singly and combined, on multiple cellular processes in fission yeast. The two dr...
متن کاملSystematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth
Target of rapamycin complex 1 (TORC1), which controls growth in response to nutrients, promotes ageing in multiple organisms. The fission yeast Schizosaccharomyces pombe emerges as a valuable genetic model system to study TORC1 function and cellular ageing. Here we exploited the combinatorial action of rapamycin and caffeine, which inhibit fission yeast growth in a TORC1-dependent manner. We sc...
متن کاملDnm1p-dependent peroxisome fission requires Caf4p, Mdv1p and Fis1p.
Yeast peroxisomes multiply by fission. Fission requires two dynamin-related proteins, Dnm1p and Vps1p. Using an in vivo fission assay, we show that Dnm1p-dependent peroxisome fission requires Fis1p, Caf4p and Mdv1p. Fluorescence microscopy of cells expressing GFP-tagged Caf4p and Mdv1p revealed that their association with peroxisomes relies on Fis1p. Vps1p-dependent peroxisome fission occurs in...
متن کاملInhibition of TORC1 signaling and increased lifespan: gained in translation?
(DR) is a well-known intervention to slow down the aging of cells and organisms. Although the molecular mechanisms by which DR prolongs lifespan are poorly understood, the Target of Rapamycin Complex 1 (TORC1) signaling pathway that controls protein translation, autophagy and mitochondrial function, among other growth-related processes, is considered a main player mediating DR effects in divers...
متن کاملMff functions with Pex11pβ and DLP1 in peroxisomal fission
PEROXISOMAL DIVISION COMPRISES THREE STEPS elongation, constriction, and fission. Translocation of dynamin-like protein 1 (DLP1), a member of the large GTPase family, from the cytosol to peroxisomes is a prerequisite for membrane fission; however, the molecular machinery for peroxisomal targeting of DLP1 remains unclear. This study investigated whether mitochondrial fission factor (Mff), which ...
متن کامل