Mitochondria are semi-autonomous organelles of prokaryotic origin that are postulated to have been acquired by eukaryotic cells through an early endosymbiotic event. Except for their main role in energy production, they are also implicated in fundamental cellular processes, including ion homeostasis, lipid metabolism, and initiation of apoptotic cell death. Perturbed mitochondrial function has been correlated with severe human pathologies such as type-2 diabetes, cardiovascular, and neurodegenerative diseases. Thus, proper mitochondrial physiology is a prerequisite for health and survival. Cells have developed sophisticated and elaborate mechanisms to adapt to stress conditions and alterations in metabolic demands, by regulating mitochondrial number and function. Hence, the generation of new and the removal of damaged or unwanted mitochondria are highly regulated processes that need to be accurately coordinated for the maintenance of mitochondrial and cellular homeostasis. Here, we survey recent research findings that advance our understanding and highlight the importance of the underlying molecular mechanisms. Abbreviations AGO2, argonaute 2; AMPK, AMP-activated protein kinase; ATFS1, activating transcription factor associated with stress 1; Atg32, autophagyrelated 32; Bcl-2, B-cell lymphoma 2; BCL2L13, Bcl-2-like 13; Bnip3, Bcl-2/adenovirus E1B 19kDa-interacting protein 3; Bnip3L/Nix, Bnip3-like/NIP3-like protein X; CCCP, carbonyl cyanide m-chlorophenyl hydrazone; CerS1, ceramide synthase 1; CL, cardiolipin; COXIV, cytochorome C oxidase subunit IV; CREB, cAMP response element-binding protein; DAF-16, abnormal DAuer Formation 16; DCT-1, DAF-16/ FOXO controlled germline tumor-affecting 1; DRP1, dynamin-related protein; ER, endoplasmic reticulum; ERRα, estrogen-related receptor alpha; FOXO, forkhead box O; FUNDC1, FUN14 domain-containing 1; GABARAP, GABA(A) receptor-associated protein; GABP, GA-binding protein transcription factor; GCN5L1, general control of amino acid synthesis 6-like 1; HO-1, heme oxygenase-1; ILS, insulin-like signaling; IMM, inner mitochondrial membrane; IMS, intermembrane space; KEAP1, Kelch-Like ECH-associated protein 1; LC3-II, lipidated form of LC3; LC3, light chain 3; LIR, LC3-interacting region; MAPK, mitogen-activated protein kinase; Mba1, multi-copy Bypass of AFG3; MDVs, mitochondrial-derived vesicles; MFN2, mitofusin 2; miRNA, micro RNA; MPP, mitochondrial processing peptidase; MtCK, mitochondrial creatine kinase; mtDNA, mitochondrial DNA; MTHFD2, methylenetetrahydrofolate dehydrogenase (NADP + dependent) 2; mTOR, mechanistic target of rapamycin; NAC, nascent polypeptide-associated complex; NBR1, neighbor of BRCA 1 gene 1; NDP52, nuclear dot protein 52 kDa; NDPK-D, nucleoside diphosphatate kinase-D; NFE2L, nuclear factor erythroid 2-like; NRF, nuclear respiratory factor; OMM, outer mitochondrial membrane; OPA1, optic atrophy 1; p62, nucleoporin 62; PARIS, Parkin-interacting substrate; PARL, presenilin-associated rhomboid-like protease; PGAM-5, phosphoglycerate mutase homolog-5; PGC1α...

Low oxygen availability, a condition known as hypoxia, is a common feature of various pathologies including stroke, ischemic heart disease, and cancer. Hypoxia adaptation requires coordination of intricate pathways and mechanisms such as hypoxia-inducible factors (HIFs), the unfolded protein response (UPR), mTOR, and autophagy. Recently, great effort has been invested toward elucidating the interplay between hypoxia-induced autophagy and cancer cell metabolism. Although novel types of selective autophagy have been identified, including mitophagy, pexophagy, lipophagy, ERphagy and nucleophagy among others, their potential interface with hypoxia response mechanisms remains poorly understood. Autophagy activation facilitates the removal of damaged cellular compartments and recycles components, thus promoting cell survival. Importantly, tumor cells rely on autophagy to support self-proliferation and metastasis; characteristics related to poor disease prognosis. Therefore, a deeper understanding of the molecular crosstalk between hypoxia response mechanisms and autophagy could provide important insights with relevance to cancer and hypoxia-related pathologies. Here, we survey recent findings implicating selective autophagy in hypoxic responses, and discuss emerging links between these pathways and cancer pathophysiology.

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