P53 regulates mitochondrial biogenesis via transcriptionally induction of mitochondrial ribosomal protein L12

Abstract

The well-documented tumor suppressor p53 is also a major stress response factor for its diverse regulation on cellular energetics. However, the effect of p53 on mitochondrial biogenesis, which plays a predominant role in response to the elevated energy demands, appears to be pleiotropic in various conditions and has not reached agreement. Mitochondrial ribosomal protein L12 (MRPL12), reported as a bi-functional protein for its roles in both mitochondrial ribosomes and transcriptional complexes, is a core regulatory component in mitochondrial biogenesis. Here we proved that MRPL12 is transcriptionally regulated by p53. Furthermore, the p53/MRPL12 regulation of mitochondria is part of the signaling pathway that maintains the basal mitochondrial content and positively coordinates the mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) in response to metabolic perturbation. Since p53 serves as the‘Guardian of the Genome’, our findings may revealed a new mechanism underlying the conditions when more ATP is warranted to maintain the genome integrity and cell survival. Therefore the pharmacological intervention or metabolic modulation (e.g., through fasting or exercise) of the p53/MRPL12 pathway promises to be a therapeutic approach that can safeguard health.