Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function

Abstract

Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. Cyclin D1 abundance thus coordinates nuclear DNA synthesis and mitochondrial function.mitochondria ͉ phosphorylation

Cyclin D1 Functions in Cell Migration

“…8 In addition to regulating the cell cycle, cyclin D1 regulates angiogenesis, lipogenesis, and mitochondrial function. [9][10][11][12] Notably, cyclin D1 has a function in transcriptional control that does not involve CDKs. 13 This function of cyclin D1, which has been reviewed recently, 2 involves promoter recruitment of histone deacetylases (HDACs) and histone methyltransferases including SUV39 and HP1.…”

A hyperfused mitochondrial state achieved at G 1 –S regulates cyclin E buildup and entry into S phase

“…In a round of cell cycle, mitochondrial oxidative capacity is greater at late G 1 than early G 1 (3), and reduction of mitochondrial ATP production blocks G 1 -to-S phase progression in flies (4). Cell cycle regulators controlling G 1 -S transition of the cell cycle are also known to affect mitochondrial function and/or shape (5,6).…”

MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan

“…Several recent studies show a link between cellular metabolism and cell cycle progression (Mitra et al 2009;Sarsour et al 2010;Sarsour et al 2008;Venkatesha et al 2010;Wang et al 2006). Cyclin D1 and E coordinate cell cycle progression with mitochondrial metabolism and functions (Mitra et al 2009;Wang et al 2006).…”

“…Cyclin D1 and E coordinate cell cycle progression with mitochondrial metabolism and functions (Mitra et al 2009;Wang et al 2006). Likewise, MnSOD dependent regulation of transition between quiescence and the proliferative cycle was associated with cyclin D1 and cyclin B1 protein levels (Sarsour et al 2008); absence of MnSOD activity negatively impacts mitochondrial morphology and functions, which inhibits quiescent NHFs entry into the proliferative cycle ).…”