Sladowska 2021 PLoS Biol
Sladowska M, Turek M, Kim MJ, Drabikowski K, Mussulini BHM, Mohanraj K, Serwa RA, Topf U, Chacinska A (2021) Proteasome activity contributes to pro-survival response upon mild mitochondrial stress in Caenorhabditis elegans. PLoS Biol 19:3001302. |
Sladowska Maria, Turek Michal, Kim Min-Ji, Drabikowski Krzysztof, Mussulini Ben Hur Marins, Mohanraj Karthik, Serwa Remigiusz A, Topf Ulrike, Chacinska Agnieszka (2021) PLoS Biol
Abstract: Defects in mitochondrial function activate compensatory responses in the cell. Mitochondrial stress that is caused by unfolded proteins inside the organelle induces a transcriptional response (termed the βmitochondrial unfolded protein responseβ [UPRmt]) that is mediated by activating transcription factor associated with stress 1 (ATFS-1). The UPRmt increases mitochondrial protein quality control. Mitochondrial dysfunction frequently causes defects in the import of proteins, resulting in the accumulation of mitochondrial proteins outside the organelle. In yeast, cells respond to mistargeted mitochondrial proteins by increasing activity of the proteasome in the cytosol (termed the βunfolded protein response activated by mistargeting of proteinsβ [UPRam]). The presence and relevance of this response in higher eukaryotes is unclear. Here, we demonstrate that defects in mitochondrial protein import in Caenorhabditis elegans lead to proteasome activation and life span extension. Both proteasome activation and life span prolongation partially depend on ATFS-1, despite its lack of influence on proteasomal gene transcription. Importantly, life span prolongation depends on the fully assembled proteasome. Our data provide a link between mitochondrial dysfunction and proteasomal activity and demonstrate its direct relevance to mechanisms that promote longevity.
β’ Bioblast editor: Reiswig R
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Aging;senescence
Organism: Caenorhabditis elegans
Preparation: Isolated mitochondria
Coupling state: OXPHOS
Pathway: N, S, CIV, ROX
HRR: Oxygraph-2k
2021-08