Selective mitochondrial autophagy or mitophagy is an evolutionarily conserved cellular process that selectively degrades superfluous, damaged, and dysfunctional mitochondria. This process is believed to be a mitochondrial quality control system crucial for intracellular homeostasis. Recently, researchers developed a range of methods to induce mitophagy and a variety of assays to monitor this process. With these new methods, the research on mitophagy has been developed rapidly. In particular, some key receptors and regulatory factors in fungi have been identified, which provides a basis for further understanding of the mechanism of this process. Although it has been studied extensively in the model yeast Saccharomyces cerevisiae , mitophagy in pathogenic fungi remains poorly understood. However recent studies have shown that mitophagy is involved in the regulation of pathogenicity of pathogenic fungi, which greatly increases the importance of mitophagy. Therefore, it is necessary to review the current research on mitophagy in order to provide an accurate understanding of mitophagy and promote mitophagy research in the pathogenic fungi.
Chinopoulos, C. and Adam-Vizi, V. (2010) Mitochondria as ATP Consumers in Cellular Pathology. Biochimica et Biophysica Acta, 1802, 221-227. https://doi.org/10.1016/j.bbadis.2009.08.008
McBride, H.M., Neuspiel, M. and Wasiak S. (2006) Mitochondria: More than Just a Powerhouse. Current Biology, 16, 551-560. https://doi.org/10.1016/j.cub.2006.06.054
Osellame, L.D., Blacker, T.S. and Duchen, M.R. (2012) Cellular and Molecular Mechanisms of Mitochondrial Function. Best Practice & Research Clinical Endocrinology & Metabolism, 26, 711-723. https://doi.org/10.1016/j.beem.2012.05.003
Zorov, D.B., Juhaszova, M. and Sollott, S.J. (2014) Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release. Physiological Reviews, 94, 909-950. https://doi.org/10.1152/physrev.00026.2013
Youle, R.J. and Narendra, D.P (2011) Mechanisms of Mitophagy. Nature Reviews Molecular Cell Biology, 12, 9-14. https://doi.org/10.1038/nrm3028
Fukuda, T. and Kanki, T. (2018) Mechanisms and Physiological Roles of Mitophagy in Yeast. Molecules and Cells, 41, 35-44. https://doi.org/10.14348/molcells.2018.2214
Ding, W.X. and Yin, X.M. (2012) Mitophagy: Mechanisms, Pathophysiological Roles, and Analysis. Biological Chemistry, 393, 547-564. https://doi.org/10.1515/hsz-2012-0119
Kanki, T., Furukawa, K. and Yamashita, S. (2015) Mitophagy in Yeast: Molecular Mechanisms and Physiological Role. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research, 1853, 2756-2765. https://doi.org/10.1016/j.bbamcr.2015.01.005
Novak, I. (2012) Mitophagy: A Complex Mechanism of Mitochondrial Removal. Antioxidants & Redox Signaling, 17, 794-802. https://doi.org/10.1089/ars.2011.4407
Feng, Y.C., He, D., Yao, Z.Y. and Klionsky, D.J. (2014) The Machinery of Macroautophagy. Cell Research, 24, 24-41. https://doi.org/10.1038/cr.2013.168
Klionsky, D.J. (2005) The Molecular Machinery of Autophagy: Unanswered Questions. Journal of Cell Science, 118, 7-18. https://doi.org/10.1242/jcs.01620
Kurihara, Y., Kanki, T., Aoki, Y., Hirota, Y., Saigusa, T. and Uchiumi, T. (2012) Mitophagy Plays an Essential Role in Reducing Mitochondrial Production of Reactive Oxygen Species and Mutation of Mitochondrial DNA by Maintaining Mitochondrial Quantity and Quality in Yeast. Journal of Biological Chemistry, 287, 3265-3272. https://doi.org/10.1074/jbc.M111.280156
Parzych, K.R. and Klionsky, D.J. (2014) An Overview of Autophagy: Morphology, Mechanism, and Regulation. Antioxidants & Redox Signaling, 20, 460-473. http://doi.org/10.1089/ars.2013.5371
Yang, Z. and Klionsky, D.J. (2009) An Overview of the Molecular Mechanism of Autophagy. In: Levine, B., Yoshimori, T. and Deretic, V., Eds., Autophagy in Infection and Immunity, Current Topics in Microbiology and Immunology, Vol. 335, Springer, Berlin, Heidelberg, 1-32. https://doi.org/10.1007/978-3-642-00302-8_1
Kershaw, M.J. and Talbot, N.J. (2009) Genome-Wide Functional Analysis Reveals That Infection-Associated Fungal Autophagy Is Necessary for Rice Blast Disease. Proceedings of the National Academy of Sciences of the United States of America, 106, 15967-15972. https://doi.org/10.1073/pnas.0901477106
Khan, I.A., Lu, J.-P., Liu, X.-H., Rehman, A. and Lin, F.-C. (2012) Multifunction of Autophagy-Related Genes in Filamentous Fungi. Microbiological Research, 167, 339-345. https://doi.org/10.1016/j.micres.2012.01.004
Kou, Y.J., He, Y.L., Qui, J.H., Shu, Y.Z., Yang, F.F., Deng, Y.Z. and Naqvi, N.I. (2019) Mitochondrial Dynamics and Mitophagy Are Necessary for Proper Invasive Growth in Rice Blast. Molecular Plant Pathology, 20, 1147-1162. https://doi.org/10.1111/mpp.12822
Tadokoro, T., Kikuma, T. and Kitamoto, K. (2015) Functional Analysis of AoAtg11 in Selective Autophagy in the Filamentous Fungus Aspergillus oryzae. Fungal Biology, 119, 560-567. https://doi.org/10.1016/j.funbio.2015.03.001
Wagner-Vogel, G., Lammer, F., Kamper, J. and Basse, C.W. (2015) Uniparental Mitochondrial DNA Inheritance Is Not Affected in Ustilago Maydis Deltaatg11 Mutants Blocked in Mitophagy. BMC Microbiology, 15, Article No. 23. https://doi.org/10.1186/s12866-015-0358-z
Wang, J.J., Peng, Y.J., Ding, J.L., Feng, M.G. and Ying, S.H. (2020) Mitochondrial Fission Is Necessary for Mitophagy, Development and Virulence of the Insect Pathogenic Fungus Beauveria bassiana. Journal of Applied Microbiology, 129, 411-421. https://doi.org/10.1111/jam.14619
Muller, M., Lu, K. and Reichert, A.S. (2015) Mitophagy and Mitochondrial Dynamics in Saccharomyces cerevisiae. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research, 1853, 2766-2774. https://doi.org/10.1016/j.bbamcr.2015.02.024
Nagi, M., Tanabe, K., Nakayama, H., Ueno, K., Yamagoe, S., Umeyama, T., Ohno, H. and Miyazaki, Y. (2016) Iron-Depletion Promotes Mitophagy to Maintain Mitochondrial Integrity in Pathogenic Yeast Candida glabrata. Autophagy, 12, 1259-1271. https://doi.org/10.1080/15548627.2016.1183080
He, Y.L., Deng, Y.Z. and Naqvi, N.I. (2013) Atg24-Assisted Mitophagy in the Foot Cells Is Necessary for Proper Asexual Differentiation in Magnaporthe oryzae. Autophagy, 9, 1818-1827. https://doi.org/10.4161/auto.26057
Henkel, V., Schürmanns, L., Brunner, M., Hamann, A. and Osiewacz, H.D. (2020) Role of Sorting Nexin PaATG24 in Autophagy, Aging and Development of Podospora anserina. Mechanisms of Ageing and Development, 186, Article ID: 111211. https://doi.org/10.1016/j.mad.2020.111211
Levchenko, M., Lorenzi, I. and Dudek, J. (2016) The Degradation Pathway of the Mitophagy Receptor Atg32 Is Re-Routed by a Posttranslational Modification. PLoS ONE, 11, e0168518. https://doi.org/10.1371/journal.pone.0168518
Cui, L.F., Zhao, H., Yin, Y.J., Liang, C., Mao, X.L., Liu, Y.Z., Yu, Q.L. and Li, M.C. (2019) Function of Atg11 in Non-Selective Autophagy and Selective Autophagy of Candida albicans. Biochemical and Biophysical Research Communications, 516, 1152-1158. https://doi.org/10.1016/j.bbrc.2019.06.148
Bhatia-Kissova, I. and Camougrand, N. (2010) Mitophagy in Yeast: Actors and Physiological Roles. FEMS Yeast Research, 10, 1023-1034. https://doi.org/10.1111/j.1567-1364.2010.00659.x
Furukawa, K., Innokentev, A. and Kanki, T. (2019) Regulatory Mechanisms of Mitochondrial Autophagy: Lessons from Yeast. Frontiers in Plant Science, 10, 1479. https://doi.org/10.3389/fpls.2019.01479
Kanki, T., Wang, K., Cao, Y., Baba, M. and Klionsky, D.J. (2009) Atg32 Is a Mitochondrial Protein That Confers Selectivity during Mitophagy. Developmental Cell, 17, 98-109. https://doi.org/10.1016/j.devcel.2009.06.014
Okamoto, K., Kondo-Okamoto, N. and Ohsumi, Y. (2009) Mitochondria-Anchored Receptor Atg32 Mediates Degradation of Mitochondria via Selective Autophagy. Developmental Cell, 17, 87-97. https://doi.org/10.1016/j.devcel.2009.06.013
Kikuma, T., Tadokoro, T., Maruyama, J. and Kitamoto, K. (2017) AoAtg26, a Putative Sterol Glucosyltransferase, Is Required for Autophagic Degradation of Peroxisomes, Mitochondria, and Nuclei in the Filamentous Fungus Aspergillus oryzae. Bioscience, Biotechnology, and Biochemistry, 81, 384-395. https://doi.org/10.1080/09168451.2016.1240603
Nieto-Jacobo, F., Pasch, D. and Basse C.W. (2012) The Mitochondrial Dnm1-Like Fission Component Is Required for lga2-Induced Mitophagy but Dispensable for Starvation-Induced Mitophagy in Ustilago maydis. Eukaryotic Cell, 11, 1152-1166. https://doi.org/10.1128/EC.00115-12
Kissova, I., Deffieu, M., Manon, S. and Camougrand, N. (2004) Uth1p is Involved in the Autophagic Degradation of Mitochondria. Journal of Biological Chemistry, 279, 39068-39074. https://doi.org/10.1074/jbc.M406960200
Camougrand, N., Kissova, I., Salin, B. and Devenish, R.J. (2008) Chapter 8 Monitoring Mitophagy in Yeast. In: Klionsky, D.J., Ed., Autophagy: Lower Eukaryotes and Non-Mammalian Systems, Part A, Academic Press, Cambridge, Massachusetts, 89-107. https://doi.org/10.1016/S0076-6879(08)03208-4
Chakraborty, J., Caicci, F., Roy, M. and Ziviani, E. (2020) Investigating Mitochondrial Autophagy by Routine Transmission Electron Microscopy: Seeing Is Believing? Pharmacological Research, 160, Article ID: 105097. https://doi.org/10.1016/j.phrs.2020.105097
Dolman, N.J., Chambers, K.M., Mandavilli B., Batchelor, R.H. and Janes, M.S. (2013) Tools and Techniques to Measure Mitophagy Using Fluorescence Microscopy. Autophagy, 9, 1653-1662. https://doi.org/10.4161/auto.24001
Tanabe, K. and Nagi, M. (2018) Monitoring of Iron Depletion-Induced Mitophagy in Pathogenic Yeast. In: Hattori, N. and Saiki, S., Eds., Mitophagy, Methods in Molecular Biology, Vol. 1759, Humana Press, New York, 161-172. https://doi.org/10.1007/7651_2017_40
Farre, J.C., Burkenroad, A., Burnett, S.F. and Subramani, S. (2013) Phosphorylation of Mitophagy and Pexophagy Receptors Coordinates Their Interaction with Atg8 and Atg11. EMBO Reports, 14, 441-449. https://doi.org/10.1038/embor.2013.40
Mijaljica, D., Prescott, M. and Devenish, R.J. (2011) A Fluorescence Microscopy Assay for Monitoring Mitophagy in the Yeast Saccharomyces cerevisiae. Journal of Visualized Experiments, No. 53, e2779. https://dx.doi.org/10.3791/2779
Nagumo, S. and Okamoto, K. (2018) Investigation of Yeast Mitophagy with Fluorescence Microscopy and Western Blotting. In: Hattori, N. and Saiki, S., Eds., Mitophagy, Methods in Molecular Biology, Vol. 1759, Humana Press, New York, 71-83. https://doi.org/10.1007/7651_2017_11
Eiyama, A. and K. Okamoto (2017) Assays for Mitophagy in Yeast. In: Mokranjac, D. and Perocchi, F., Eds., Mitochondria, Methods in Molecular Biology, Vol. 1567. Humana Press, New York, 337-347. https://doi.org/10.1007/978-1-4939-6824-4_20
Malina, C., Larsson, C. and Nielsen, J. (2018) Yeast Mitochondria: An Overview of Mitochondrial Biology and the Potential of Mitochondrial Systems Biology. FEMS Yeast Research, 18, Article ID: foy040. https://doi.org/10.1093/femsyr/foy040
Gatica, D., Lahiri, V. and Klionsky, D.J. (2018) Cargo Recognition and Degradation by Selective Autophagy. Nature Cell Biology, 20, 233-242. https://doi.org/10.1038/s41556-018-0037-z
Aihara, M. and Schwarz, T.L. (2014) Tor and the Sin3-Rpd3 Complex Regulate Expression of the Mitophagy Receptor Protein Atg32 in Yeast. Journal of Cell Science, 127, 3184-3196. https://doi.org/10.1242/jcs.153254
Roetzer, A., Gratz, N., Kovarik, P. and Schuller, C. (2010) Autophagy Supports Candida glabrata Survival during Phagocytosis. Cell Microbiology, 12, 199-216. https://doi.org/10.1111/j.1462-5822.2009.01391.x
Liu, X.H. and Lin, F.C. (2008) Investigation of the Biological Roles of Autophagy in Appressorium Morphogenesis in Magnaporthe oryzae. Journal of Zhejiang University-Science B, 9, 793-796. https://doi.org/10.1631/jzus.B0860013
Xie, Z.P., Nair, U. and Klionsky, D.J. (2008) Atg8 Controls Phagophore Expansion during Autophagosome Formation. Molecular Biology of the Cell, 19, 3290-3298. https://doi.org/10.1091/mbc.e07-12-1292
Matscheko, N., Mayrhofer, P., Rao, Y., Beier, V. and Wollert, T. (2019) Atg11 tethers Atg9 Vesicles to Initiate Selective Autophagy. PLoS Biology, 17, e3000377. https://doi.org/10.1371/journal.pbio.3000377
Suzuki, H. and Noda, N.N. (2018) Biophysical Characterization of Atg11, a Scaffold Protein Essential for Selective Autophagy in Yeast. FEBS Open Biology, 8, 110-116. https://doi.org/10.1002/2211-5463.12355
Zientara-Rytter, K. and Subramani, S. (2020) Mechanistic Insights into the Role of Atg11 in Selective Autophagy. Journal of Molecular Biology, 432, 104-122. https://doi.org/10.1016/j.jmb.2019.06.017
Kikuma, T., Takayuki, T., Maruyama, J. and Katsuhiko, K. (2006) Functional Analysis of the ATG8 Homologue Aoatg8 and Role of Autophagy in Differentiation and Germination in Aspergillus oryzae. Eukaryot Cell, 5, 1328-1336. https://doi.org/10.1128/EC.00024-06
Liu, T.B., Liu, X.H., Lu, J.P, Zhang, L., Min, H. and Lin, F.C. (2010) The Cysteine Protease MoAtg4 Interacts with MoAtg8 and Is Required for Differentiation and Pathogenesis in Magnaporthe oryzae. Autophagy, 6, 74-85. https://doi.org/10.4161/auto.6.1.10438
Liu, T.B., Liu, X.H., Lu, J.P., Zhang, L., Min, H. and Lin F.C. (2010) The Autophagy Genes atg8 and atg1 Affect Morphogenesis and Pathogenicity in Ustilago maydis. Molecular Plant Pathology, 11, 463-478. https://doi.org/10.1111/j.1364-3703.2010.00620.x
Ying, S.H., Liu, J., Chu, X.L., Xie, X.Q. and Feng, M.G. (2016) The Autophagy-Related Genes BbATG1 and BbATG8 Have Different Functions in Differentiation, Stress Resistance and Virulence of Mycopathogen Beauveria bassiana. Science Reports, 6, Article No. 26376. https://doi.org/10.1038/srep26376
Kikuma, T. and Kitamoto, K. (2011) Analysis of Autophagy in Aspergillus oryzae by Disruption of Aoatg13, Aoatg4, and Aoatg15 Genes. FEMS Microbiology Letter, 316, 61-69. https://doi.org/10.1111/j.1574-6968.2010.02192.x
Kanki, T. and Klionsky, D.J. (2010) The Molecular Mechanism of Mitochondria Autophagy in Yeast. Molecular Microbiology, 75, 795-800. https://doi.org/10.1111/j.1365-2958.2009.07035.x
Reggiori, F. and Klionsky, D.J. (2013) Autophagic Processes in Yeast: Mechanism, Machinery and Regulation. Genetics, 194, 341-361. https://doi.org/10.1534/genetics.112.149013
Scott, I. and Youle, R.J. (2010) Mitochondrial Fission and Fusion. Essays in Biochemistery, 47, 85-98. https://doi.org/10.1042/bse0470085
Mendl, N., Occhipinti, A., Muller, M., Wild, P., Dikic, I. and Reichert, A.S. (2011) Mitophagy in Yeast Is Independent of Mitochondrial Fission and Requires the Stress Response Gene WHI2. Journal of Cell Science, 124, 1339-1350. https://doi.org/10.1242/jcs.076406
Merz, S., Hammermeister, M., Altman, K., Durr, M. and Westermann, B. (2007) Molecular Machinery of Mitochondrial Dynamics in Yeast. Biology Chemical, 388, 917-926. https://doi.org/10.1515/BC.2007.110
Mao, K. and Klionsky, D.J. (2013) Mitochondrial Fission Facilitates Mitophagy in Saccharomyces cerevisiae. Autophagy, 9, 1900-1911. https://doi.org/10.4161/auto.25804
Jiang, J.C., Stumpferl, S.W. and Jazwinski, S.M. (2019) Dual Roles of Mitochondrial Fusion Gene FZO1 in Yeast Age Asymmetry and in Longevity Mediated by a Novel ATG32-Dependent Retrograde Response. Biogerontology, 20, 93-107. https://doi.org/10.1007/s10522-018-9779-z