Inhibition of peroxisome fission, but not mitochondrial fission, increases yeast chronological lifespan

Abstract

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.

Keywords: Fis1; chronological aging; fission; mitochondria; peroxisome; yeast.

Figure 1.

Peroxisome and mitochondrial fission defects in various yeast mutant strains. Fluorescence microscopy images showing mitochondrial and peroxisome morphology in Δvps1Δfis1 (A), Δvps1Δfis1::FIS1 (B) and Δvps1Δfis1::FIS1-PEX15 (C) cells. Cells were grown until the mid-exponential growth phase on MM containing 2% glucose. Peroxisomes are marked by DsRED-SKL and mitochondria by mitoGFP.

Figure 2.

Exclusive sorting of Fis1 to peroxisomes does not result in lifespan extension. (A) Chronological lifespans of Δvps1, Δvps1Δfis1, Δvps1Δfis1::FIS1 and Δvps1Δfis1::FIS1-PEX15 cells. Data represent mean ± SEM from at least 2 experiments. (B) Statistical analysis for mean and maximum lifespans of strains presented in panel A. *, p < 0.001.

Figure 3.

Increased peroxisome fission does not affect the CLS. (A) Mitochondrial and peroxisomal morphology in Δvps1 and Δvps1 FIS1-PEX15 cells. Peroxisomes were labeled with DsRED-SKL and mitochondria by mitoGFP. (B) Chronological lifespan analysis of Δvps1 and Δvps1 FIS1-PEX15 cells. Data represent mean ± SEM from at least 2 experiments.

Figure 4.

FIS1 deletion in Δpex3 cells has no effect on the CLS. (A) Fluorescence microscopy of Δpex3 and Δpex3Δfis1 cells producing DsRED-SKL or mitoGFP. (B). Chronological lifespan experiment of Δpex3 and Δpex3Δfis1 cells. Data represent mean ± SEM from at least 2 experiments.