Exploring a novel biological role of the master energy homeostasis regulator PGC1 a as a potential modifier of mitochondrial function and senescence

Alteration of the energy metabolism and mitochondrial dysfunction are known features of senescence and manipulating mitochondrial function through caloric restriction prolongs survival. The master energy regulator PGC1 a plays a pivotal role in controlling the antioxidant response and the energy metabolism homeostasis through transcriptional co-activation of genes involved in mitochondrial biogenesis and function. It therefore plays key egulatory metabolic functions in muscles, liver, adipocytes and neurons. PGC1a-dependent regulatory pathways are down-regulated in age and age-related diseases (muscle wasting, metabolic and neurodegenerative disorders). In addition to the well-characterised transcriptional function, PGC1a contains a putative RNA recognition motif which has not been investigated. We recently discovered that PGC1a directly binds RNA and drives the nuclear export of some PGC1a-activated mRNAs encoding mitochondrial-related proteins in human embryonic kidney cells (unpublished data) potentially linking its novel nuclear export function to the transcripts it co-activates.