Abstract
The accumulation of functionally impaired mitochondria is a key event in aging. Previous works with the fungal aging model Podospora anserina demonstrated pronounced age-dependent changes of mitochondrial morphology and ultrastructure, as well as alterations of transcript and protein levels, including individual proteins of the oxidative phosphorylation (OXPHOS). The identified protein changes do not reflect the level of the whole protein complexes as they function in-vivo. In the present study, we investigated in detail the age-dependent changes of assembled mitochondrial protein complexes, using complexome profiling. We observed pronounced age-depen-dent alterations of the OXPHOS complexes, including the loss of mitochondrial respiratory supercomplexes (mtRSCs) and a reduction in the abundance of complex I and complex IV. Additionally, we identified a switch from the standard complex IV-dependent respiration to an alternative respiration during the aging of the P. anserina wild type. Interestingly, we identified proteasome components, as well as endoplasmic reticulum (ER) proteins, for which the recruitment to mitochondria appeared to be increased in the mitochondria of older cultures. Overall, our data demonstrate pronounced age-dependent alterations of the protein complexes involved in energy transduction and suggest the induction of different non-mitochondrial salvage pathways, to counteract the age-dependent mitochondrial impairments which occur during aging.
Highlights
Biological aging is commonly described as a process associated with the time-dependent decline of physiological functions and the accumulation of cellular and molecular damage [1,2,3]
Our data demonstrate pronounced age-dependent alterations of the protein complexes involved in energy transduction and suggest the induction of different non-mitochondrial salvage pathways, to counteract the age-dependent mitochondrial impairments which occur during aging
The pronounced age-associated reorganization of the mitochondrial DNA (mtDNA) of P. anserina, resulting in the deletion of large parts of the mtDNA, suggested that severe changes of the mitochondrial transcriptome and proteome occur during aging [29,30,31,32,33]
Summary
Biological aging is commonly described as a process associated with the time-dependent decline of physiological functions and the accumulation of cellular and molecular damage [1,2,3]. Mitochondria have been demonstrated to play a central role in aging [4,5,6,7,8,9] These organelles are involved in a number of essential cellular processes, including the synthesis of iron/sulfur clusters, amino acid, lipids, and in energy transduction leading to the production of ATP. One model organism with a strong mitochondrial etiology of aging is the ascomycete Podospora anserina [12,13,14] This filamentous fungus is characterized by a limited lifespan. The typical lamellar cristae ultrastructure changes and forms vesicles [18,19] This age-dependent structural reorganization is concurrent with the dissociation of F1Fo-ATP synthase dimers [20]. Age-dependent fragmentation of mitochondria and reorganization of the inner membrane were reported for other organisms, from yeast to humans [17,23,24,25,26,27,28]
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