title: Akt3 knockdown induces mitochondrial dysfunction in human cancer cells.
abstract: Akt/PKB plays a pivotal role in cell proliferation and survival. However, the isotype-specific roles of Akt in mitochondrial function have not been fully addressed. In this study, we explored the role of Akt in mitochondrial function after stable knockdown of the Akt isoforms in EJ human bladder cancer cells. We found that the mitochondrial mass was significantly increased in the Akt1- and Akt3-knockdown cells, and this increase was accompanied by an increase in TFAM and NRF1. Akt2 knockdown did not cause a similar effect. Interestingly, Akt3 knockdown also led to severe structural defects in the mitochondria, an increase in doxorubicin-induced senescence, and impairment of cell proliferation in galactose medium. Consistent with these observations, the mitochondrial oxygen consumption rate was significantly reduced in the Akt3-knockdown cells. An Akt3 deficiency-induced decrease in mitochondrial respiration was also observed in A549 lung cancer cells. Collectively, these results suggest that the Akt isoforms play distinct roles in mitochondrial function and that Akt3 is critical for proper mitochondrial respiration in human cancer cells.
authors.affiliation: Department of Biochemistry, College of Medicine, Dong-A University, Busan 607-714, Republic of Korea Institute of Convergence Bio-Health, Dong-A University, Busan 607-714, Republic of Korea.
authors.forename: Minjee
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Dong-A University, Busan 607-714, Republic of Korea Institute of Convergence Bio-Health, Dong-A University, Busan 607-714, Republic of Korea.
authors.forename: Young Yeon
authors.initials: YY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Dong-A University, Busan 607-714, Republic of Korea Institute of Convergence Bio-Health, Dong-A University, Busan 607-714, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jee
authors.affiliation: Department of Pharmacology, School of Medicine, Pusan National University, Yangsan-si 602-739, Republic of Korea.
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
authors.affiliation: Institute of Convergence Bio-Health, Dong-A University, Busan 607-714, Republic of Korea Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
authors.forename: Na Young
authors.initials: NY
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry, College of Medicine, Dong-A University, Busan 607-714, Republic of Korea Institute of Convergence Bio-Health, Dong-A University, Busan 607-714, Republic of Korea.
authors.forename: Jee-Hyun
authors.initials: JH
authors.lastname: Um
authors.affiliation: Department of Biochemistry, College of Medicine, Dong-A University, Busan 607-714, Republic of Korea Institute of Convergence Bio-Health, Dong-A University, Busan 607-714, Republic of Korea yunj@dau.ac.kr.
authors.forename: Jeanho
authors.initials: J
authors.lastname: Yun
mesh_terms: D000072283:A549 Cells; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C494918:AKT1 protein, human; C494921:AKT2 protein, human; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Akt3; isoform-specific function; mitochondria