Trauma Research Center, Fourth Medical Center of the Chinese PLA General Hospital, Beijing, People's Republic of China.
Department of Burn Surgery, Changhai Hospital, Navy Medical University, Shanghai, People's Republic of China.
Autophagy. 2021 Feb;17(2):385-401. doi: 10.1080/15548627.2020.1725377. Epub 2020 Feb 12.
The structural integrity and functional stability of organelles are prerequisites for the viability and responsiveness of cells. Dysfunction of multiple organelles is critically involved in the pathogenesis and progression of various diseases, such as chronic obstructive pulmonary disease, cardiovascular diseases, infection, and neurodegenerative diseases. In fact, those organelles synchronously present with evident structural derangement and aberrant function under exposure to different stimuli, which might accelerate the corruption of cells. Therefore, the quality control of multiple organelles is of great importance in maintaining the survival and function of cells and could be a potential therapeutic target for human diseases. Organelle-specific autophagy is one of the major subtypes of autophagy, selectively targeting different organelles for quality control. This type of autophagy includes mitophagy, pexophagy, reticulophagy (endoplasmic reticulum), ribophagy, lysophagy, and nucleophagy. These kinds of organelle-specific autophagy are reported to be beneficial for inflammatory disorders by eliminating damaged organelles and maintaining homeostasis. In this review, we summarized the recent findings and mechanisms covering different kinds of organelle-specific autophagy, as well as their involvement in various diseases, aiming to arouse concern about the significance of the quality control of multiple organelles in the treatment of inflammatory diseases. ABCD3: ATP binding cassette subfamily D member 3; AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; AMBRA1: autophagy and beclin 1 regulator 1; AMPK: AMP-activated protein kinase; ARIH1: ariadne RBR E3 ubiquitin protein ligase 1; ATF: activating transcription factor; ATG: autophagy related; ATM: ATM serine/threonine kinase; BCL2: BCL2 apoptosis regulator; BCL2L11/BIM: BCL2 like 11; BCL2L13: BCL2 like 13; BECN1: beclin 1; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CANX: calnexin; CAT: catalase; CCPG1: cell cycle progression 1; CHDH: choline dehydrogenase; COPD: chronic obstructive pulmonary disease; CSE: cigarette smoke exposure; CTSD: cathepsin D; DDIT3/CHOP: DNA-damage inducible transcript 3; DISC1: DISC1 scaffold protein; DNM1L/DRP1: dynamin 1 like; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2S1/eIF2α: eukaryotic translation initiation factor 2 alpha kinase 3; EMD: emerin; EPAS1/HIF-2α: endothelial PAS domain protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FBXO27: F-box protein 27; FKBP8: FKBP prolyl isomerase 8; FTD: frontotemporal dementia; FUNDC1: FUN14 domain containing 1; G3BP1: G3BP stress granule assembly factor 1; GBA: glucocerebrosidase beta; HIF1A/HIF1: hypoxia inducible factor 1 subunit alpha; IMM: inner mitochondrial membrane; LCLAT1/ALCAT1: lysocardiolipin acyltransferase 1; LGALS3/Gal3: galectin 3; LIR: LC3-interacting region; LMNA: lamin A/C; LMNB1: lamin B1; LPS: lipopolysaccharide; MAPK8/JNK: mitogen-activated protein kinase 8; MAMs: mitochondria-associated membranes; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MFN1: mitofusin 1; MOD: multiple organelles dysfunction; MTPAP: mitochondrial poly(A) polymerase; MUL1: mitochondrial E3 ubiquitin protein ligase 1; NBR1: NBR1 autophagy cargo receptor; NLRP3: NLR family pyrin domain containing 3; NUFIP1: nuclear FMR1 interacting protein 1; OMM: outer mitochondrial membrane; OPTN: optineurin; PD: Parkinson disease; PARL: presenilin associated rhomboid like; PEX3: peroxisomal biogenesis factor 3; PGAM5: PGAM family member 5; PHB2: prohibitin 2; PINK1: PTEN induced putative kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RETREG1/FAM134B: reticulophagy regulator 1; RHOT1/MIRO1: ras homolog family member T1; RIPK3/RIP3: receptor interacting serine/threonine kinase 3; ROS: reactive oxygen species; RTN3: reticulon 3; SEC62: SEC62 homolog, preprotein translocation factor; SESN2: sestrin2; SIAH1: siah E3 ubiquitin protein ligase 1; SNCA: synuclein alpha; SNCAIP: synuclein alpha interacting protein; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; TICAM1/TRIF: toll-like receptor adaptor molecule 1; TIMM23: translocase of inner mitochondrial membrane 23; TNKS: tankyrase; TOMM: translocase of the outer mitochondrial membrane; TRIM: tripartite motif containing; UCP2: uncoupling protein 2; ULK1: unc-51 like autophagy activating kinase; UPR: unfolded protein response; USP10: ubiquitin specific peptidase 10; VCP/p97: valosin containing protein; VDAC: voltage dependent anion channels; XIAP: X-linked inhibitor of apoptosis; ZNHIT3: zinc finger HIT-type containing 3.
细胞器的结构完整性和功能稳定性是细胞存活和响应性的前提条件。多种细胞器的功能障碍与慢性阻塞性肺疾病、心血管疾病、感染和神经退行性疾病等各种疾病的发病机制和进展密切相关。事实上,在受到不同刺激时,这些细胞器会同时出现明显的结构紊乱和异常功能,这可能加速细胞的腐败。因此,维持细胞的存活和功能,对多种细胞器进行质量控制非常重要,这可能成为人类疾病的潜在治疗靶点。
细胞器特异性自噬是自噬的主要亚型之一,可选择性地针对不同细胞器进行质量控制。这种自噬包括线粒体自噬、过氧化物酶体自噬(又称pexophagy)、内质网自噬(又称 reticulophagy)、核糖体自噬、溶酶体自噬和核自噬。这些种类的细胞器特异性自噬被报道通过消除受损的细胞器并维持内环境平衡,有利于炎症性疾病。
在本综述中,我们总结了涵盖不同种类的细胞器特异性自噬及其在各种疾病中的作用的最新发现和机制,旨在引起人们对炎症性疾病治疗中多种细胞器质量控制的重要性的关注。