title: Parkin ubiquitinates mTOR to regulate mTORC1 activity under mitochondrial stress.
abstract: mTORC1, a kinase complex that is considered a master regulator of cellular growth and proliferation, is regulated by many extra- and intracellular signals. Among these signals, mitochondrial status is known to have an impact on the effects of mTORC1 on cell growth and survival. However, how mitochondrial status affects mTORC1 activity, notably the molecular link, is not fully elucidated. Here, we found that Parkin can interact with and ubiquitinate mTOR. We also identified K2066 and K2306 as Parkin-dependent and mitochondrial stress-induced mTOR ubiquitination residues. This ubiquitination by Parkin is required for maintenance of mTORC1 activity under mitochondrial stress. With regard to the physiological meaning of mTORC1 activity under mitochondrial stress, we suggest that mTORC1 plays a pro-survival role.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Mi Nam
authors.initials: MN
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Heeyoon
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Ara
authors.initials: A
authors.lastname: Koh
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea.
authors.forename: Yong Ryoul
authors.initials: YR
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea. Electronic address: sungho@postech.ac.kr.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000031:analogs & derivatives / Q000633:toxicity; D057809:HEK293 Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000076223:Regulatory-Associated Protein of mTOR; D020123:Sirolimus / Q000633:toxicity; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Mitochondrial stress; Parkin; Ubiquitination; mTOR; mTORC1