MDM2 and mitochondrial function: One complex intersection

被引:13
|
作者
Rubio-Patino, Camila [1 ,2 ]
Trotta, Andrew Paul [1 ,2 ]
Chipuk, Jerry Edward [1 ,2 ,3 ,4 ,5 ,6 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Oncol Sci, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Tisch Canc Inst, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
[3] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
[4] Icahn Sch Med Mt Sinai, Dept Dermatol, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
[5] Icahn Sch Med Mt Sinai, Dept Dermatol, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
[6] Icahn Sch Med Mt Sinai, Diabet Obes & Metab Inst, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA
关键词
Apoptosis; Bioenergetics; Complex I; Electron transport chain; MDM2; Mitochondria; Oncogene; p53; Tumor suppressor; DEPENDENT PROTEIN-KINASE; DNA-ENCODED SUBUNITS; P53; PROTEIN; OXIDATIVE-PHOSPHORYLATION; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; ELECTRON-TRANSPORT; GENE AMPLIFICATION; OVEREXPRESSION; CANCER;
D O I
10.1016/j.bcp.2018.10.032
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Decades of research reveal that MDM2 participates in cellular processes ranging from macro-molecular metabolism to cancer signaling mechanisms. Two recent studies uncovered a new role for MDM2 in mitochondrial bioenergetics. Through the negative regulation of NDUFS1 (NADH:ubiquinone oxidoreductase 75 kDa Fe-S protein 1) and MT-ND6 (NADH dehydrogenase 6), MDM2 decreases the function and efficiency of Complex I (CI). These observations propose several important questions: (1) Where does MDM2 affect CI activity? (2) What are the cellular consequences of MDM2-mediated regulation of CI? (3) What are the physiological implications of these interactions? Here, we will address these questions and position these observations within the MDM2 literature.
引用
收藏
页码:14 / 20
页数:7
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