Loss of p16INK4A stimulates aberrant mitochondrial biogenesis through a CDK4/Rb-independent pathway

作者：Ethika Tyagi, Bin Liu, Chelsea Li, Tong Liu, Jared Rutter, Douglas Grossman · 发表于：Oncotarget · 年份：2017 · DOI：10.18632/oncotarget.19862 · 被引用次数：30 · 研究领域：Cancer-related Molecular Pathways、Cancer, Hypoxia, and Metabolism、Cancer Research and Treatments

// Ethika Tyagi 1,* , Bin Liu 1,* , Chelsea Li 1 , Tong Liu 1 , Jared Rutter 3,4 and Douglas Grossman 1,2 1 The Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake, Utah, USA 2 The Department of Dermatology, University of Utah Health Sciences Center, Salt Lake, Utah, USA 3 The Department of Biochemistry, University of Utah Health Sciences Center, Salt Lake, Utah, USA 4 The Howard Hughes Medical Institute, University of Utah Health Sciences Center, Salt Lake, Utah, USA * These authors have contributed equally to this work Correspondence to: Douglas Grossman, email: // Keywords : p16, mitochondria, CDK4, migration, fibroblast Received : May 24, 2017 Accepted : July 09, 2017 Published : August 03, 2017 Abstract The tumor suppressor p16INK4A (p16) inhibits cell cycle progression through the CDK4/Rb pathway. We have previously shown that p16 regulates cellular oxidative stress, independent of its role in cell cycle control. We investigated whether loss of p16 had a direct impact on the mitochondria. We found that p16-null primary mouse fibroblasts (PMFs) displayed increased mitochondrial mass and expression of mitochondrial respiratory subunit proteins compared to wild-type (WT) PMFs. These findings in p16-null PMFs were associated with increased expression of the mitochondrial biogenesis transcription factors PRC and TFAM. On the other hand, p16-deficient PMFs demonstrated reduced mitochondrial respiration capacity consistent with electron microscopy f...