title: Mitofusin 2-deficiency suppresses cell proliferation through disturbance of autophagy.
abstract: Mitofusin2 (Mfn2), a mitochondrial outer membrane protein serving primarily as a mitochondrial fusion protein, has multiple functions in regulating cell biological processes. Defects of Mfn2 were found in diabetes, obesity, and neurodegenerative diseases. In the present study, we found that knockdown of Mfn2 by shRNA led to impaired autophagic degradation, inhibited mitochondrial oxygen consumption rate and cell glycolysis, reduced ATP production, and suppressed cell proliferation. Inhibition of autophagic degradation mimicked Mfn2-deficiency mediated cell proliferation suppression, while enhancement of autophagosome maturation restored the suppressed cell proliferation by Mfn2-deficiency. Thus, our findings revealed the role of Mfn2 in regulating cell proliferation and mitochondrial metabolism, and shed new light on understanding the mechanisms of Mfn2 deficiency related diseases.
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
mesh_terms: D001343:Autophagy; D049109:Cell Proliferation; D020558:GTP Phosphohydrolases / Q000172:deficiency*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000172:deficiency*
chemical_list: D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human