A comprehensive glossary of autophagy-related molecules and processes (2(nd) edition)

Life Sciences Institute, and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Autophagy (Impact Factor: 11.75). 11/2011; 7(11):1273-94. DOI: 10.4161/auto.7.11.17661
Source: PubMed


The study of autophagy is rapidly expanding, and our knowledge of the molecular mechanism and its connections to a wide range of physiological processes has increased substantially in the past decade. The vocabulary associated with autophagy has grown concomitantly. In fact, it is difficult for readers--even those who work in the field--to keep up with the ever-expanding terminology associated with the various autophagy-related processes. Accordingly, we have developed a comprehensive glossary of autophagy-related terms that is meant to provide a quick reference for researchers who need a brief reminder of the regulatory effects of transcription factors and chemical agents that induce or inhibit autophagy, the function of the autophagy-related proteins, and the roles of accessory components and structures that are associated with autophagy.

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Available from: Daniel J Klionsky
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    • "Assembly of genes involved in mitochondrial dynamic gene categories comprising mitochondrial fusion and fission, mitochondrial DNA replication and biogenesis regulation, mitochondrial repair and protection systems, macroautophagy initiation and nucleation regulation, autophagosome expansion and ATG conjugation, syntaxin/SNAREs [SNAP (Soluble NSF Attachment Protein) REceptor], selective macroautophagy (including mitophagy), autophagosome trafficking facilitation, and lysosomal fusion, lysosomal biogenesis, proteasome assembly, E1 ubiquitin activators, E2 ubiquitin conjugation enzymes, E3 ubiquitin ligases, ubiquitin, etc, and heat shock proteins70/40/27/22kDa also were analyzed using a combination of resources as a template, including the HUGO gene name consortium (, NCBI tools, ENSEMBLE genome browser, by hand search of the literature, and autophagy genes determined largely based around the 2nd edition glossary of autophagy terms and processes (Klionsky et al. 2011) (Figure 7 and File S3). Determination of lens epithelial (EC and EQ regions) or fiber cell (FP and FC regions) expression preference for a given nuclear encoded mitochondrial regulatory transcript was determined by Figure 2 Identification of differentially expressed transcripts. "
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    ABSTRACT: The mature eye lens contains a surface layer of epithelial cells called the lens epithelium that require a functional mitochondrial population to maintain the homeostasis and transparency of the entire lens. The lens epithelium overlies a core of terminally differentiated fiber cells that must degrade their mitochondria to achieve lens transparency. These distinct mitochondrial populations make the lens a useful model system to identify those genes that regulate the balance between mitochondrial homeostasis and elimination. Here we used an RNA sequencing and bioinformatics approach to identify the transcript levels of all genes expressed by distinct regions of the lens epithelium and maturing fiber cells of the embryonic Gallus gallus (chicken) lens. Our analysis detected over 15,000 unique transcripts expressed by the embryonic chicken lens. Of these, over 3000 transcripts exhibited significant differences in expression between lens epithelial cells and fiber cells. Multiple transcripts coding for separate mitochondrial homeostatic and degradation mechanisms were identified to exhibit preferred patterns of expression in lens epithelial cells that require mitochondria relative to lens fiber cells that require mitochondrial elimination. These included differences in the expression levels of metabolic (DUT, PDK1, SNPH), autophagy (ATG3, ATG4B, BECN1, FYCO1, WIPI1), and mitophagy (BNIP3L/NIX, BNIP3, PARK2, p62/SQSTM1) transcripts between lens epithelial cells and lens fiber cells. These data provide a comprehensive window into all genes transcribed by the lens and those mitochondrial regulatory and degradation pathways that function to maintain mitochondrial populations in the lens epithelium and to eliminate mitochondria in maturing lens fiber cells.
    Full-text · Article · Jun 2014 · G3-Genes Genomes Genetics
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    • "As HRES-1/Rab41–121 showed the greatest colocalization with LC3 without starvation or Rapa treatment, this truncated isoform may not act through promoting but rather retaining the association of mitochondria with LC3+ lysosomes. Alternatively, the strong association of HRES-1/Rab41–121 with LC3 may reflect its targeting for degradation through the autophagy-lysosome pathway [15], [30], which has been also documented for other proteins such as misfolded superoxide dismutase [31] and truncated Cln6 [32]. "
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    ABSTRACT: HRES-1/Rab4 is a small GTPase that regulates endocytic recycling. It has been colocalized to mitochondria and the mechanistic target of rapamycin (mTOR), a suppressor of autophagy. Since the autophagosomal membrane component microtubule-associated protein light chain 3 (LC3) is derived from mitochondria, we investigated the impact of HRES-1/Rab4 on the formation of LC3(+) autophagosomes, their colocalization with HRES-1/Rab4 and mitochondria, and the retention of mitochondria during autophagy induced by starvation and rapamycin. HRES-1/Rab4 exhibited minimal baseline colocalization with LC3, which was enhanced 22-fold upon starvation or 6-fold upon rapamycin treatment. Colocalization of HRES-1/Rab4 with mitochondria was increased >2-fold by starvation or rapamycin. HRES-1/Rab4 overexpression promoted the colocalization of mitochondria with LC3 upon starvation or rapamycin treatment. A dominant-negative mutant, HRES-1/Rab4(S27N) had reduced colocalization with LC3 and mitochondria upon starvation but not rapamycin treatment. A constitutively active mutant, HRES-1/Rab4(Q72L) showed diminished colocalization with LC3 but promoted the partitioning of mitochondria with LC3 upon starvation or rapamycin treatment. Phosphorylation-resistant mutant HRES-1/Rab4(S204Q) showed diminished colocalization with LC3 but increased partitioning to mitochondria. A newly discovered C-terminally truncated native isoform, HRES-1/Rab4(1-121), showed enhanced localization to LC3 and mitochondria without starvation or rapamycin treatment. HRES-1/Rab4(1-121) increased the formation of LC3(+) autophagosomes in resting cells, while other isoforms promoted autophagosome formation upon starvation. HRES-1/Rab4, HRES-1/Rab4(1-121), HRES-1/Rab4(Q72L) and HRES-1/Rab4(S204Q) promoted the accumulation of mitochondria during starvation. The specificity of HRES-1/Rab4-mediated mitochondrial accumulation is indicated by its abrogation by dominant-negative HRES-1/Rab4(S27N) mutation. The formation of interconnected mitochondrial tubular networks was markedly enhanced by HRES-1/Rab4(Q72L) upon starvation, which may contribute to the retention of mitochondria during autophagy. The present study thus indicates that HRES-1/Rab4 regulates autophagy through promoting the formation of LC3(+) autophagosomes and the preservation of mitochondria.
    Full-text · Article · Jan 2014 · PLoS ONE
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    • "Of these, many are part of the core autophagy machinery essential for the formation of canonical autophagosomes (see below), whereas others function only in different selective autophagy pathways (Mizushima et al., 2011). For more details regarding the molecular mechanisms of autophagy, we refer the reader to other excellent reviews (Klionsky et al., 2011; Mizushima et al., 2011). "
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    ABSTRACT: Peroxisomes are remarkably dynamic organelles that participate in a diverse array of cellular processes, including the metabolism of lipids and reactive oxygen species. In order to regulate peroxisome function in response to changing nutritional and environmental stimuli, new organelles need to be formed and superfluous and dysfunctional organelles have to be selectively removed. Disturbances in any of these processes have been associated with the etiology and progression of various congenital neurodegenerative and age-related human disorders. The aim of this review is to critically explore our current knowledge of how peroxisomes are degraded in mammalian cells and how defects in this process may contribute to human disease. Some of the key issues highlighted include the current concepts of peroxisome removal, the peroxisome quality control mechanisms, the initial triggers for peroxisome degradation, the factors for dysfunctional peroxisome recognition, and the regulation of peroxisome homeostasis. We also dissect the functional and mechanistic relationship between different forms of selective organelle degradation and consider how lysosomal dysfunction may lead to defects in peroxisome turnover. In addition, we draw lessons from studies on other organisms and extrapolate this knowledge to mammals. Finally, we discuss the potential pathological implications of dysfunctional peroxisome degradation for human health.
    Full-text · Article · Jun 2013 · Frontiers in Physiology
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