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Aging of biological systems is accompanied by degeneration of mitochondrial functions. Different pathways are active to counteract the processes which lead to mitochondrial dysfunction. Mitochondrial dynamics, the fission and fusion of mitochondria, is one of these quality control pathways. Mitophagy, the controlled degradation of mitochondria, is another one. Here we show that these pathways are linked. A double deletion mutant of Saccharomyces cerevisiae in which two essential components of the fission and fusion machinery, Dnm1 and Mgm1, are simultaneously ablated, contain wild-type like filamentous mitochondria, but are characterized by impaired respiration, an increased sensitivity to different stressors, increased mitochondrial protein carbonylation, and a decrease in mitophagy and replicative lifespan. These data show that a balanced mitochondrial dynamics and not a filamentous mitochondrial morphotype per se is the key for a long lifespan and demonstrate a cross-talk between two different mitochondrial quality control pathways.
Mitochondrial respiratory supercomplexes (mtRSCs) are stoichiometric assemblies of electron transport chain (ETC) complexes in the inner mitochondrial membrane. They are hypothesized to regulate electron flow, the generation of reactive oxygen species (ROS) and to stabilize ETC complexes. Using the fungal ageing model Podospora anserina, we investigated the impact of homologues of the Saccharomyces cerevisiae respiratory supercomplex factors 1 and 2 (termed PaRCF1 and PaRCF2) on mtRSC formation, fitness and lifespan. Whereas PaRCF2’s role seems negligible, ablation of PaRCF1 alters size of monomeric complex IV, reduces the abundance of complex IV-containing supercomplexes, negatively affects vital functions and shortens lifespan. PaRcf1 overexpression slightly prolongs lifespan, though without appreciably influencing ETC organization. Overall, our results identify PaRCF1 as necessary yet not sufficient for mtRSC formation and demonstrate that PaRCF1-dependent stability of complex IV and associated supercomplexes is highly relevant for maintenance of the healthy lifespan in a eukaryotic model organism.
Maintenance of mitochondria is achieved by several mechanisms, including the regulation of mitochondrial proteostasis. The matrix protease CLPXP, involved in protein quality control, has been implicated in ageing and disease. However, particularly due to the lack of knowledge of CLPXP's substrate spectrum, only little is known about the pathways and mechanisms controlled by this protease. Here we report the first comprehensive identification of potential mitochondrial CLPXP in vivo interaction partners and substrates using a combination of tandem affinity purification and differential proteomics. This analysis reveals that CLPXP in the fungal ageing model Podospora anserina is mainly associated with metabolic pathways in mitochondria, e.g. components of the pyruvate dehydrogenase complex and the tricarboxylic acid cycle as well as subunits of electron transport chain complex I. These data suggest a possible function of mitochondrial CLPXP in the control and/or maintenance of energy metabolism. Since bioenergetic alterations are a common feature of neurodegenerative diseases, cancer, and ageing, our data comprise an important resource for specific studies addressing the role of CLPXP in these adverse processes.