Mitophagy in Yeast Occurs through a Selective Mechanism

Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-2216, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 10/2008; 283(47):32386-93. DOI: 10.1074/jbc.M802403200
Source: PubMed


The regulation of mitochondrial degradation through autophagy is expected to be a tightly controlled process, considering
the significant role of this organelle in many processes ranging from energy production to cell death. However, very little
is known about the specific nature of the degradation process. We developed a new method to detect mitochondrial autophagy
(mitophagy) by fusing the green fluorescent protein at the C terminus of two endogenous mitochondrial proteins and monitored
vacuolar release of green fluorescent protein. Using this method, we screened several atg mutants and found that ATG11, a gene that is essential only for selective autophagy, is also essential for mitophagy. In addition, we found that mitophagy
is blocked even under severe starvation conditions, if the carbon source makes mitochondria essential for metabolism. These
findings suggest that the degradation of mitochondria is a tightly regulated process and that these organelles are largely
protected from nonspecific autophagic degradation.

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    • "Regarding pexophagy in methylotrophic yeasts and S. cerevisiae, Atg11 has been identified as an essential scaffold protein for PAS formation [32] [33]. This is consistent with findings in mitophagy, which also highlighted the central role of Atg11 in the process [34]. "
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    ABSTRACT: Pexophagy, selective degradation of peroxisomes via autophagy, is the main system for reducing organelle abundance. Elucidation of the molecular machinery of pexophagy has been pioneered in studies of the budding yeast Saccharomyces cerevisiae and the methylotrophic yeasts Pichia pastoris and Hansenula polymorpha. Recent analyses using these yeasts have elucidated the molecular machineries of pexophagy, especially in terms of the interactions and modifications of the so-called adaptor proteins required for guiding autophagic membrane biogenesis on the organelle surface. Based on the recent findings, functional relevance of pexophagy and another autophagic pathway, mitophagy (selective autophagy of mitochondria), is discussed. We also discuss the physiological importance of pexophagy in these yeast systems. This article is part of a Special Issue entitled: Peroxisomes.
    Biochimica et Biophysica Acta 09/2015; DOI:10.1016/j.bbamcr.2015.09.023 · 4.66 Impact Factor
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    • "In yeast, Uth1, a mitochondrial outer membrane protein, as well as Aup1, a mitochondrial phosphatase, were reported to be critical for mitophagy (Kanki and Klionsky 2008; Kissova et al. 2004). Recently, systematic screens for components involved in this process revealed several additional components required for this selective type of autophagy including Atg11, Atg20, Atg24, Atg32, Atg33 (Kanki and Klionsky 2008, 2009; Okamoto et al. 2009). Atg32 is of particular interest as it was reported to act as a receptor in mitophagy. "
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    ABSTRACT: Ageing is accompanied by the accumulation of damaged molecules in cells due to the injury produced by external and internal stressors. Among them, reactive oxygen species produced by cell metabolism, inflammation or other enzymatic processes are considered key factors. However, later research has demonstrated that a general mitochondrial dysfunction affecting electron transport chain activity, mitochondrial biogenesis and turnover, apoptosis, etc., seems to be in a central position to explain ageing. This key role is based on several effects from mitochondrial-derived ROS production to the essential maintenance of balanced metabolic activities in old organisms. Several studies have demonstrated caloric restriction, exercise or bioactive compounds mainly found in plants, are able to affect the activity and turnover of mitochondria by increasing biogenesis and mitophagy, especially in postmitotic tissues. Then, it seems that mitochondria are in the centre of metabolic procedures to be modified to lengthen life- or health-span. In this review we show the importance of mitochondria to explain the ageing process in different models or organisms (e.g. yeast, worm, fruitfly and mice). We discuss if the cause of aging is dependent on mitochondrial dysfunction of if the mitochondrial changes observed with age are a consequence of events taking place outside the mitochondrial compartment.
    Biogerontology 06/2015; 16(5). DOI:10.1007/s10522-015-9585-9 · 3.29 Impact Factor
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    • "We selected strains deficient in ATG1 and ATG5, genes coding for proteins with a role in autophagy and also mitophagy [30], and ATG11, a gene coding for a protein required for mitophagy but not for general autophagy [31]. Wt and autophagy deficient strains expressing Parkin or GFP only (control) were treated with 3 mM H 2 O 2 . "
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    ABSTRACT: Mutations in Parkin, an E3 ubiquitin ligase, are associated to autosomal recessive Parkinson´s disease (PD). Parkin has been mainly implicated, along with Pink1, in mitochondrial autophagy in response to stress. In this study, a yeast model was developed to analyse the biological function of human Parkin. We observed that Parkin increases yeast chronological lifespan and oxidative stress resistance, through a mitochondrial-dependent pathway. Moreover, in response to H2O2, Parkin translocate to mitochondria, leading to a higher mitochondrial degradation. Parkin-induced H2O2 resistance is dependent on the autophagic pathway and on the mitochondrial protein Por1p. Although expression of Pink1 induces an H2O2 resistance phenotype similar to Parkin, co-expression of both proteins does not result in a synergistic effect. Concerning H2O2 resistance, this may indicate that these two proteins independently affect the same pathway. Altogether, this work establishes a yeast model for Parkin, which may provide new insights on Parkin function and potential mechanisms of pathogenicity. Copyright © 2015. Published by Elsevier Inc.
    Experimental Cell Research 02/2015; 333(1). DOI:10.1016/j.yexcr.2015.02.018 · 3.25 Impact Factor
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