The mechanism of mammalian mitochondrial quality control system



mammals; mitochondrial dynamics; mitochondrial Autophagy; protein quality control


 The mitochondria perform an essential role in cellular metabolism by acting as a cellular energy powerhouse. It is also involved in several biological processes such as cell metabolism, stress signaling, calcium homeostasis, and reactive oxygen species(ROS) and apoptosis. Maintaining cellular physiological function is strongly dependent on mitochondrial quality control. mitochondrial malfunction will lead to various disorders. For this review, we evaluate the current understanding of the molecular mechanism of mitochondria quality control, which might also serve as an asset for organisms' health and the prevention of disease


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Marcel V Alavi, and Nico Fuhrmann, 'Dominant Optic Atrophy, Opa1, and Mitochondrial Quality Control: Understanding Mitochondrial Network Dynamics', Molecular neurodegeneration, 8 (2013), 1-12.

Michael J Baker, Philipp A Lampe, Diana Stojanovski, Anne Korwitz, Ruchika Anand, Takashi Tatsuta, and Thomas Langer, 'Stress‐Induced Oma 1 Activation and Autocatalytic Turnover Regulate Opa 1‐Dependent Mitochondrial Dynamics', The EMBO journal, 33 (2014), 578-93.

JP Bernardini, M Lazarou, and Grant Dewson, 'Parkin and Mitophagy in Cancer', Oncogene, 36 (2017), 1315-27.

Piotr Bragoszewski, Agnieszka Gornicka, Malgorzata E Sztolsztener, and Agnieszka Chacinska, 'The Ubiquitin-Proteasome System Regulates Mitochondrial Intermembrane Space Proteins', Molecular and cellular biology, 33 (2013), 2136-48.

Martin D Brand, 'The Sites and Topology of Mitochondrial Superoxide Production', Experimental gerontology, 45 (2010), 466-72.

Kausik Chakraborty, Manal Chatila, Jyoti Sinha, Qiaoyun Shi, Bernhard C Poschner, Martin Sikor, Guoxin Jiang, Don C Lamb, F Ulrich Hartl, and Manajit Hayer-Hartl, 'Chaperonin-Catalyzed Rescue of Kinetically Trapped States in Protein Folding', Cell, 142 (2010), 112-22.

Fatima Zahra Chakrama, Stéphanie Seguin-Py, Jaclyn Nicole Le Grand, Annick Fraichard, Régis Delage-Mourroux, Gilles Despouy, Valérie Perez, Michèle Jouvenot, and Michaël Boyer-Guittaut, 'Gabarapl1 (Gec1) Associates with Autophagic Vesicles', Autophagy, 6 (2010), 495-505.

Hsiuchen Chen, Anne Chomyn, and David C Chan, 'Disruption of Fusion Results in Mitochondrial Heterogeneity and Dysfunction', Journal of Biological Chemistry, 280 (2005), 26185-92.

Lucia Cilenti, Camilla T Ambivero, Nathan Ward, Emad S Alnemri, Doris Germain, and Antonis S Zervos, 'Inactivation of Omi/Htra2 Protease Leads to the Deregulation of Mitochondrial Mulan E3 Ubiquitin Ligase and Increased Mitophagy', Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1843 (2014), 1295-307.

J Thomas Cribbs, and Stefan Strack, 'Reversible Phosphorylation of Drp1 by Cyclic Amp‐Dependent Protein Kinase and Calcineurin Regulates Mitochondrial Fission and Cell Death', EMBO reports, 8 (2007), 939-44.

Rafal Dutkiewicz, Brenda Schilke, Helena Knieszner, William Walter, Elizabeth A Craig, and Jaroslaw Marszalek, 'Ssq1, a Mitochondrial Hsp70 Involved in Iron-Sulfur (Fe/S) Center Biogenesis: Similarities to and Differences from Its Bacterial Counterpart', Journal of Biological Chemistry, 278 (2003), 29719-27.

Hasnaa A Elfawy, and Biswadeep Das, 'Crosstalk between Mitochondrial Dysfunction, Oxidative Stress, and Age Related Neurodegenerative Disease: Etiologies and Therapeutic Strategies', Life sciences, 218 (2019), 165-84.

Kirstin D Elgass, Elizabeth A Smith, Mark A LeGros, Carolyn A Larabell, and Michael T Ryan, 'Analysis of Er–Mitochondria Contacts Using Correlative Fluorescence Microscopy and Soft X-Ray Tomography of Mammalian Cells', Journal of cell science, 128 (2015), 2795-804.

Anbo Gao, Jinyong Jiang, Feng Xie, and Linxi Chen, 'Bnip3 in Mitophagy: Novel Insights and Potential Therapeutic Target for Diseases of Secondary Mitochondrial Dysfunction', Clinica Chimica Acta, 506 (2020), 72-83.

Doris Germain, 'Ubiquitin‐Dependent and‐Independent Mitochondrial Protein Quality Controls: Implications in Ageing and Neurodegenerative Diseases', Molecular microbiology, 70 (2008), 1334-41.

Andrew W Greene, Karl Grenier, Miguel A Aguileta, Stephanie Muise, Rasoul Farazifard, M Emdadul Haque, Heidi M McBride, David S Park, and Edward A Fon, 'Mitochondrial Processing Peptidase Regulates Pink1 Processing, Import and Parkin Recruitment', EMBO reports, 13 (2012), 378-85.

Anne Hamacher-Brady, and Nathan Ryan Brady, 'Mitophagy Programs: Mechanisms and Physiological Implications of Mitochondrial Targeting by Autophagy', Cellular and molecular life sciences, 73 (2016), 775-95.

Cole M Haynes, Kseniya Petrova, Cristina Benedetti, Yun Yang, and David Ron, 'Clpp Mediates Activation of a Mitochondrial Unfolded Protein Response in C. Elegans', Developmental cell, 13 (2007), 467-80.

Rostyslav Horbay, and Rostyslav Bilyy, 'Mitochondrial Dynamics During Cell Cycling', Apoptosis, 21 (2016), 1327-35.

Susanne E Horvath, and Günther Daum, 'Lipids of Mitochondria', Progress in lipid research, 52 (2013), 590-614.

Naotada Ishihara, Yuu Fujita, Toshihiko Oka, and Katsuyoshi Mihara, 'Regulation of Mitochondrial Morphology through Proteolytic Cleavage of Opa1', The EMBO journal, 25 (2006), 2966-77.

Jae‐Hoon Jeong, Jee Young An, Yong Tae Kwon, Juong G Rhee, and Yong J Lee, 'Effects of Low Dose Quercetin: Cancer Cell‐Specific Inhibition of Cell Cycle Progression', Journal of cellular biochemistry, 106 (2009), 73-82.

Seok Min Jin, Michael Lazarou, Chunxin Wang, Lesley A Kane, Derek P Narendra, and Richard J Youle, 'Mitochondrial Membrane Potential Regulates Pink1 Import and Proteolytic Destabilization by Parl', Journal of Cell Biology, 191 (2010), 933-42.

Michael Käser, and Thomas Langer, 'Protein Degradation in Mitochondria', in Seminars in cell & developmental biology (Elsevier, 2000), pp. 181-90.

Vladimir Kirkin, Trond Lamark, Yu-Shin Sou, Geir Bjørkøy, Jennifer L Nunn, Jack-Ansgar Bruun, Elena Shvets, David G McEwan, Terje H Clausen, and Philipp Wild, 'A Role for Nbr1 in Autophagosomal Degradation of Ubiquitinated Substrates', Molecular cell, 33 (2009), 505-16.

Mirko Koppen, and Thomas Langer, 'Protein Degradation within Mitochondria: Versatile Activities of Aaa Proteases and Other Peptidases', Critical reviews in biochemistry and molecular biology, 42 (2007), 221-42.

Vassilios N Kotiadis, Michael R Duchen, and Laura D Osellame, 'Mitochondrial Quality Control and Communications with the Nucleus Are Important in Maintaining Mitochondrial Function and Cell Health', Biochimica et Biophysica Acta (BBA)-General Subjects, 1840 (2014), 1254-65.

Yukiko Kuroda, Takao Mitsui, Makoto Kunishige, Masayuki Shono, Masashi Akaike, Hiroyuki Azuma, and Toshio Matsumoto, 'Parkin Enhances Mitochondrial Biogenesis in Proliferating Cells', Human molecular genetics, 15 (2006), 883-95.

Michael Lazarou, Seok Min Jin, Lesley A Kane, and Richard J Youle, 'Role of Pink1 Binding to the Tom Complex and Alternate Intracellular Membranes in Recruitment and Activation of the E3 Ligase Parkin', Developmental cell, 22 (2012), 320-33.

Stewart H Lecker, Alfred L Goldberg, and William E Mitch, 'Protein Degradation by the Ubiquitin–Proteasome Pathway in Normal and Disease States', Journal of the American Society of Nephrology, 17 (2006), 1807-19.

Youngil Lee, Hwa-Youn Lee, Rita A Hanna, and Åsa B Gustafsson, 'Mitochondrial Autophagy by Bnip3 Involves Drp1-Mediated Mitochondrial Fission and Recruitment of Parkin in Cardiac Myocytes', American journal of physiology-heart and circulatory physiology, 301 (2011), H1924-H31.

Peng Ma, Jina Yun, Hansong Deng, and Ming Guo, 'Atg1-Mediated Autophagy Suppresses Tissue Degeneration in Pink1/Parkin Mutants by Promoting Mitochondrial Fission in Drosophila', Molecular biology of the cell, 29 (2018), 3082-92.

Yuichi Matsushima, Yu-ichi Goto, and Laurie S Kaguni, 'Mitochondrial Lon Protease Regulates Mitochondrial DNA Copy Number and Transcription by Selective Degradation of Mitochondrial Transcription Factor a (Tfam)', Proceedings of the National Academy of Sciences, 107 (2010), 18410-15.

Arnaud Mourier, Elisa Motori, Tobias Brandt, Marie Lagouge, Ilian Atanassov, Anne Galinier, Gunter Rappl, Susanne Brodesser, Kjell Hultenby, and Christoph Dieterich, 'Mitofusin 2 Is Required to Maintain Mitochondrial Coenzyme Q Levels', Journal of Cell Biology, 208 (2015), 429-42.

Michael P Murphy, and Richard C Hartley, 'Mitochondria as a Therapeutic Target for Common Pathologies', Nature Reviews Drug Discovery, 17 (2018), 865-86.

Derek P Narendra, Seok Min Jin, Atsushi Tanaka, Der-Fen Suen, Clement A Gautier, Jie Shen, Mark R Cookson, and Richard J Youle, 'Pink1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin', PLoS biology, 8 (2010), e1000298.

Derek Narendra, Atsushi Tanaka, Der-Fen Suen, and Richard J Youle, 'Parkin Is Recruited Selectively to Impaired Mitochondria and Promotes Their Autophagy', Journal of cell biology, 183 (2008), 795-803.

Juliana Navarro-Yepes, Michaela Burns, Annadurai Anandhan, Oleh Khalimonchuk, Luz Maria Del Razo, Betzabet Quintanilla-Vega, Aglaia Pappa, Mihalis I Panayiotidis, and Rodrigo Franco, 'Oxidative Stress, Redox Signaling, and Autophagy: Cell Death Versus Survival', Antioxidants & redox signaling, 21 (2014), 66-85.

Mark Nolden, Sarah Ehses, Mirko Koppen, Andrea Bernacchia, Elena I Rugarli, and Thomas Langer, 'The M-Aaa Protease Defective in Hereditary Spastic Paraplegia Controls Ribosome Assembly in Mitochondria', Cell, 123 (2005), 277-89.

Aurélien Olichon, Laurent Baricault, Nicole Gas, Emmanuelle Guillou, Annie Valette, Pascale Belenguer, and Guy Lenaers, 'Loss of Opa1 Perturbates the Mitochondrial Inner Membrane Structure and Integrity, Leading to Cytochrome C Release and Apoptosis', Journal of Biological Chemistry, 278 (2003), 7743-46.

Anthony Orvedahl, Rhea Sumpter, Guanghua Xiao, Aylwin Ng, Zhongju Zou, Yi Tang, Masahiro Narimatsu, Christopher Gilpin, Qihua Sun, and Michael Roth, 'Image-Based Genome-Wide Sirna Screen Identifies Selective Autophagy Factors', Nature, 480 (2011), 113-17.

Hidenori Otera, Naotada Ishihara, and Katsuyoshi Mihara, 'New Insights into the Function and Regulation of Mitochondrial Fission', Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1833 (2013), 1256-68.

Hidenori Otera, Non Miyata, Osamu Kuge, and Katsuyoshi Mihara, 'Drp1-Dependent Mitochondrial Fission Via Mid49/51 Is Essential for Apoptotic Cristae Remodeling', Journal of Cell Biology, 212 (2016), 531-44.

Hidenori Otera, Chunxin Wang, Megan M Cleland, Kiyoko Setoguchi, Sadaki Yokota, Richard J Youle, and Katsuyoshi Mihara, 'Mff Is an Essential Factor for Mitochondrial Recruitment of Drp1 During Mitochondrial Fission in Mammalian Cells', Journal of Cell Biology, 191 (2010), 1141-58.

Catherine S Palmer, Laura D Osellame, David Laine, Olga S Koutsopoulos, Ann E Frazier, and Michael T Ryan, 'Mid49 and Mid51, New Components of the Mitochondrial Fission Machinery', EMBO reports, 12 (2011), 565-73.

Serhiy Pankiv, Terje Høyvarde Clausen, Trond Lamark, Andreas Brech, Jack-Ansgar Bruun, Heidi Outzen, Aud Øvervatn, Geir Bjørkøy, and Terje Johansen, 'P62/Sqstm1 Binds Directly to Atg8/Lc3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy', Journal of biological chemistry, 282 (2007), 24131-45.

Mark W Pellegrino, Amrita M Nargund, and Cole M Haynes, 'Signaling the Mitochondrial Unfolded Protein Response', Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1833 (2013), 410-16.

Oliver Rothfuss, Heike Fischer, Takafumi Hasegawa, Martina Maisel, Petra Leitner, Franziska Miesel, Manu Sharma, Antje Bornemann, Daniela Berg, and Thomas Gasser, 'Parkin Protects Mitochondrial Genome Integrity and Supports Mitochondrial DNA Repair', Human molecular genetics, 18 (2009), 3832-50.

Heide Schatten, Qing-Yuan Sun, and Randall Prather, 'The Impact of Mitochondrial Function/Dysfunction on Ivf and New Treatment Possibilities for Infertility', Reproductive Biology and Endocrinology, 12 (2014), 1-11.

Gottfried Schatz, 'The Protein Import System of Mitochondria', Journal of Biological Chemistry, 271 (1996), 31763-66.

Almas Siddiqui, Dipa Bhaumik, Shankar J Chinta, Anand Rane, Subramanian Rajagopalan, Christopher A Lieu, Gordon J Lithgow, and Julie K Andersen, 'Mitochondrial Quality Control Via the Pgc1α-Tfeb Signaling Pathway Is Compromised by Parkin Q311x Mutation but Independently Restored by Rapamycin', Journal of Neuroscience, 35 (2015), 12833-44.

Zhiyin Song, Hsiuchen Chen, Maja Fiket, Christiane Alexander, and David C Chan, 'Opa1 Processing Controls Mitochondrial Fusion and Is Regulated by Mrna Splicing, Membrane Potential, and Yme1l', Journal of Cell Biology, 178 (2007), 749-55.

Vincent Soubannier, Gian-Luca McLelland, Rodolfo Zunino, Emelie Braschi, Peter Rippstein, Edward A Fon, and Heidi M McBride, 'A Vesicular Transport Pathway Shuttles Cargo from Mitochondria to Lysosomes', Current Biology, 22 (2012), 135-41.

Aleksandr Stotland, and Roberta A Gottlieb, 'Mitochondrial Quality Control: Easy Come, Easy Go', Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1853 (2015), 2802-11.

Ayumu Sugiura, Gian‐Luca McLelland, Edward A Fon, and Heidi M McBride, 'A New Pathway for Mitochondrial Quality Control: Mitochondrial‐Derived Vesicles', The EMBO journal, 33 (2014), 2142-56.

Naoko Taguchi, Naotada Ishihara, Akihiro Jofuku, Toshihiko Oka, and Katsuyoshi Mihara, 'Mitotic Phosphorylation of Dynamin-Related Gtpase Drp1 Participates in Mitochondrial Fission', Journal of Biological Chemistry, 282 (2007), 11521-29.

Josep A Villena, 'New Insights into Pgc‐1 Coactivators: Redefining Their Role in the Regulation of Mitochondrial Function and Beyond', The FEBS journal, 282 (2015), 647-72.

Wolfgang Voos, 'Chaperone–Protease Networks in Mitochondrial Protein Homeostasis', Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1833 (2013), 388-99.

Qi-Heng Yang, Robin Church-Hajduk, Jinyu Ren, Michelle L Newton, and Chunying Du, 'Omi/Htra2 Catalytic Cleavage of Inhibitor of Apoptosis (Iap) Irreversibly Inactivates Iaps and Facilitates Caspase Activity in Apoptosis', Genes & development, 17 (2003), 1487-96.

Fei Yin, Harsh Sancheti, Zhigang Liu, and Enrique Cadenas, 'Mitochondrial Function in Ageing: Coordination with Signalling and Transcriptional Pathways', The Journal of physiology, 594 (2016), 2025-42.

Richard J Youle, and Alexander M Van Der Bliek, 'Mitochondrial Fission, Fusion, and Stress', Science, 337 (2012), 1062-65.

Wen Yue, Ziheng Chen, Haiyang Liu, Chen Yan, Ming Chen, Du Feng, Chaojun Yan, Hao Wu, Lei Du, and Yueying Wang, 'A Small Natural Molecule Promotes Mitochondrial Fusion through Inhibition of the Deubiquitinase Usp30', Cell research, 24 (2014), 482-96.

Mònica Zamora, Rosario Pardo, and Josep A Villena, 'Pharmacological Induction of Mitochondrial Biogenesis as a Therapeutic Strategy for the Treatment of Type 2 Diabetes', Biochemical pharmacology, 98 (2015), 16-28.

Tongmei Zhang, Liang Xue, Li Li, Chengyuan Tang, Zhengqing Wan, Ruoxi Wang, Jieqiong Tan, Ya Tan, Hailong Han, and Runyi Tian, 'Bnip3 Protein Suppresses Pink1 Kinase Proteolytic Cleavage to Promote Mitophagy', Journal of biological chemistry, 291 (2016), 21616-29.

Dmitry B Zorov, Magdalena Juhaszova, and Steven J Sollott, 'Mitochondrial Reactive Oxygen Species (Ros) and Ros-Induced Ros Release', Physiological reviews, 94 (2014), 909-50.



How to Cite

Khan, S. ullah, & Khan, M. U. . (2021). The mechanism of mammalian mitochondrial quality control system. Journal of Chemistry and Nutritional Biochemistry, 2(2), 59–69.