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...

The elimination of abnormal and dysfunctional cellular constituents is an essential prerequisite for nerve cells to maintain their homeostasis and proper function. This is mainly achieved through autophagy, a process that eliminates abnormal and dysfunctional cellular components, including misfolded proteins and damaged organelles. Several studies suggest that age-related decline of autophagy impedes neuronal homeostasis and, subsequently, leads to the progression of neurodegenerative disorders due to the accumulation of toxic protein aggregates in neurons. Here, we discuss the involvement of autophagy perturbation in neurodegeneration and present evidence indicating that upregulation of autophagy holds potential for the development of therapeutic interventions towards confronting neurodegenerative diseases in humans.

One-carbon metabolism (OCM) is a network of biochemical reactions delivering one-carbon units to various biosynthetic pathways. The folate cycle and methionine cycle are the two key modules of this network that regulate purine and thymidine synthesis, amino acid homeostasis, and epigenetic mechanisms. Intersection with the transsulfuration pathway supports glutathione production and regulation of the cellular redox state. Dietary intake of micronutrients, such as folates and amino acids, directly contributes to OCM, thereby adapting the cellular metabolic state to environmental inputs. The contribution of OCM to cellular proliferation during development and in adult proliferative tissues is well established. Nevertheless, accumulating evidence reveals the pivotal role of OCM in cellular homeostasis of non-proliferative tissues and in coordination of signaling cascades that regulate energy homeostasis and longevity. In this review, we summarize the current knowledge on OCM and related pathways and discuss how this metabolic network may impact longevity and neurodegeneration across species.