Regulation of the Stress-Activated Degradation of Mitochondrial Respiratory Complexes in Yeast

[EN] Repair and removal of damaged mitochondria is a key process for eukaryotic cell homeostasis. Here we investigate in the yeast model how different protein complexes of the mitochondrial electron transport chain are subject to specific degradation upon high respiration load and organelle damage. We find that the turnover of subunits of the electron transport complex I equivalent and complex III is preferentially stimulated upon high respiration rates. Particular mitochondrial proteases, but not mitophagy, are involved in this activated degradation. Further mitochondrial damage by valinomycin treatment of yeast cells triggers the mitophagic removal of the same respiratory complexes. This selective protein degradation depends on the mitochondrial fusion and fission apparatus and the autophagy adaptor protein Atg11, but not on the mitochondrial mitophagy receptor Atg32. Loss of autophagosomal protein function leads to valinomycin sensitivity and an overproduction of reactive oxygen species upon mitochondrial damage. A specific event in this selective turnover of electron transport chain complexes seems to be the association of Atg11 with the mitochondrial network, which can be achieved by overexpression of the Atg11 protein even in the absence of Atg32. Furthermore, the interaction of various Atg11 molecules via the C-terminal coil domain is specifically and rapidly stimulated upon mitochondrial damage and could therefore be an early trigger of selective mitophagy in response to the organelles dysfunction. Our work indicates that autophagic quality control upon mitochondrial damage operates in a selective manner.This work was funded by grants from Ministerio de Economia y Competitividad (BFU2011-23326) and from Ministerio de Economia, Industria y Competitividad (BFU2016-75792-R). AT-G received a pre-doctoral fellowship from Consejo Superior de Investigaciones Cientificas (JAE-Pre).Timón Gómez, A.; Sanfeliu-Redondo, D.; Pascual-Ahuir Giner, MD.; Proft, MH. (2018). Regulation of the Stress-Activated Degradation of Mitochondrial Respiratory Complexes in Yeast. Frontiers in Microbiology. 9. https://doi.org/10.3389/fmicb.2018.00106S