21 December 2011
autophagy, mitochondrion, neurodegeneration, nitrative stress, oxidative stress, redox signalling, ALS, amyotrophic lateral sclerosis, AMPK, 5′-AMP-activated protein kinase, ATG, AuTophaGy-related, BAG, Bcl-2-associated athanogene, BNIP, Bcl-2/adenovirus E18 19-kDa-interacting protein, BNIP3L, BNIP3-like, Drp1, dynamin-related protein 1, ECH, enoyl-CoA hydratase, EM, electron microscopy, ER, endoplasmic reticulum, FIP200, focal adhesion kinase family-interacting protein of 200 kDa, GABARAP, GABAA (γ-aminobutyric acid type A)-receptor-associated protein, GFP, green fluorescent protein, HIF-1, hypoxia-inducible factor 1, HNE, 4-hydroxynonenal, IκB, inhibitor of nuclear factor κB, IKKβ, IκB kinase β, IP3, inositol 1,4,5-trisphosphate, JNK1, c-Jun N-terminal kinase 1, Keap1, Kelch-like ECH-associated protein 1, LAMP, lysosome-associated membrane protein, LC3, light chain 3, LRRK2, leucine-rich repeat kinase 2, 3-MA, 3-methyladenine, mETC, mitochondrial electron-transport chain, mtDNA, mitochondrial DNA, mTOR, mammalian target of rapamycin, NAC, N-acetyl-L-cysteine, NBR1, neighbour of BRCA1 (breast cancer early-onset 1), NF-κB, nuclear factor κB, NGF, nerve growth factor, NOS, nitric oxide synthase, NOX, NADPH oxidase, Nrf2, nuclear factor-erythroid 2-related factor 2, PE, phosphatidylethanolamine, PI3K, phosphoinositide 3-kinase, PI3P, phosphatidylinositol 3-phosphate, PINK1, PTEN (phosphatase and tensin homologue deleted on chromosome 10)-induced kinase 1 , RFP, red fluorescent protein, RLS, reactive lipid species, RNS, reactive nitrogen species, ROS, reactive oxygen species, Rubicon, RUN domain- and cysteine-rich domain-containing beclin-1-interacting protein, siRNA, small interfering RNA, SOD, superoxide dismutase, TAC, transverse aortic constriction, tfLC3, tandem fluorescently tagged LC3, TIGAR, TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator, TNFα, tumour necrosis factor α, TOR, target of rapamycin, Tzb, trastuzumab, UCP, uncoupling protein, ULK, unc (unco-ordinated family member)-51-like kinase, VDAC, voltage-dependent anion channel, Vps34, vacuolar protein sorting 34
Reactive oxygen and nitrogen species change cellular responses through diverse mechanisms that are now being defined. At low levels, they are signalling molecules, and at high levels, they damage organelles, particularly the mitochondria. Oxidative damage and the associated mitochondrial dysfunction may result in energy depletion, accumulation of cytotoxic mediators and cell death. Understanding the interface between stress adaptation and cell death then is important for understanding redox biology and disease pathogenesis. Recent studies have found that one major sensor of redox signalling at this switch in cellular responses is autophagy. Autophagic activities are mediated by a complex molecular machinery including more than 30 Atg (AuTophaGy-related) proteins and 50 lysosomal hydrolases. Autophagosomes form membrane structures, sequester damaged, oxidized or dysfunctional intracellular components and organelles, and direct them to the lysosomes for degradation. This autophagic process is the sole known mechanism for mitochondrial turnover. It has been speculated that dysfunction of autophagy may result in abnormal mitochondrial function and oxidative or nitrative stress. Emerging investigations have provided new understanding of how autophagy of mitochondria (also known as mitophagy) is controlled, and the impact of autophagic dysfunction on cellular oxidative stress. The present review highlights recent studies on redox signalling in the regulation of autophagy, in the context of the basic mechanisms of mitophagy. Furthermore, we discuss the impact of autophagy on mitochondrial function and accumulation of reactive species. This is particularly relevant to degenerative diseases in which oxidative stress occurs over time, and dysfunction in both the mitochondrial and autophagic pathways play a role.