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

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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nuclear export of some PGC1a-activated mRNAs encoding mitochondrial-related proteins in human embryonic kidney cells (unpublished data) potentially linking its novel nuclear export function to the transcripts it co-activates.