title: p21(WAF¹/C¹P¹) deficiency induces mitochondrial dysfunction in HCT116 colon cancer cells.
abstract: p21(WAF1/CIP1) is a critical regulator of cell cycle progression. However, the role of p21 in mitochondrial function remains poorly understood. In this study, we examined the effect of p21 deficiency on mitochondrial function in HCT116 human colon cancer cells. We found that there was a significant increase in the mitochondrial mass of p21(-/-) HCT116 cells, as measured by 10-N-nonyl-acridine orange staining, as well as an increase in the mitochondrial DNA content. In contrast, p53(-/-) cells had a mitochondrial mass comparable to that of wild-type HCT116 cells. In addition, the expression levels of the mitochondrial biogenesis regulators PGC-1α and TFAM and AMPK activity were also elevated in p21(-/-) cells, indicating that p21 deficiency induces the rate of mitochondrial biogenesis through the AMPK-PGC-1α axis. However, the increase in mitochondrial biogenesis in p21(-/-) cells did not accompany an increase in the cellular steady-state level of ATP. Furthermore, p21(-/-) cells exhibited significant proliferation impairment in galactose medium, suggesting that p21 deficiency induces a defect in the mitochondrial respiratory chain in HCT116 cells. Taken together, our results suggest that the loss of p21 results in an aberrant increase in the mitochondrial mass and in mitochondrial dysfunction in HCT116 cells, indicating that p21 is required to maintain proper mitochondrial mass and respiratory function.
authors.affiliation: Department of Biochemistry, College of Medicine, Dong-A University, Busan, South Korea.
authors.forename: Ae Jeong
authors.initials: AJ
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jee
authors.forename: Naree
authors.initials: N
authors.lastname: Song
authors.forename: Minjee
authors.initials: M
authors.lastname: Kim
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Jeanho
authors.initials: J
authors.lastname: Yun
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D063269:Mitochondrial Turnover; D009369:Neoplasms / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases