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Figure 2. Mitochondrial quality control pathways. (A) Activation of the UPR^mt in C.elegans. Mitochondrial stress leads to inhibition of TOM/TIM-mediated mitochondrial import of ATFS-1. This allows ATFS-1 to re-localize to the nucleus where it proceeds to activate a transcriptional response aimed at restoring mitochondrial homeostasis. (B) Activation of the integrated stress response (ISR) in mammalian cells. The protease OMA1 cleaves Dele1 in response to mitochondrial stress. Dele1 activates HRI in the cytosol which phosphorylates eIF2a leading to activation of the ISR. (C) Regulators of mitochondrial autophagy. PINK1 accumulates on the outer membrane of dysfunctional mitochondria where it recruits the E3 ubiquitin ligase Parkin. Parkin-mediated ubiquitination leads to binding of adaptor proteins such as OPTN and LC3 on the growing autophagosome membrane. Mitophagy receptors in the outer mitochondrial membrane facilitate ubiquitin independent autophagic sequestration of mitochondria (Created with BioRender.com).