Mitochondrial biogenesis: An update

Abstract

In response to the energy demand triggered by developmental signals and environmental stressors, the cells launch the mitochondrial biogenesis process. This is a self-renewal route, by which new mitochondria are generated from the ones already existing. Recently, considerable progress has been made in deciphering mitochondrial biogenesis-related proteins and genes that function in health and in pathology-related circumstances. However, an outlook on the intracellular mechanisms shared by the main players that drive mitochondrial biogenesis machinery is still missing. Here, we provide such a view by focusing on the following issues: (a) the role of mitochondrial biogenesis in homeostasis of the mitochondrial mass and function, (b) the signalling pathways beyond the induction/promotion, stimulation and inhibition of mitochondrial biogenesis and (c) the therapeutic applications aiming the repair and regeneration of defective mitochondrial biogenesis (in ageing, metabolic diseases, neurodegeneration and cancer). The review is concluded by the perspectives of mitochondrial medicine and research.

Keywords: PGC-1α; ageing; cancer; metabolic diseases; mtDNA; neurodegeneration; nuclear respiratory factors; transcription factor A.

Figure 1

Mitochondrial biogenesis in brief: the central role of PGC‐1α activation and the contribution of proteins encoded by both nuclear and mitochondrial genomes (nDNA and mtDNA) to enhance the mitochondrial proteins content. AMPK, 5' adenosine monophosphate‐activated protein kinase; ERR, the oestrogen‐related receptor; NRF, the nuclear respiratory factor; PGC‐1α, the peroxisome proliferator‐activated receptor‐γ coactivator‐1α; SIRT‐1, the silent information regulator‐1; TFAM, the transcription factor α; TIM 23, translocase