Mitochondrial mistranslation is modulated by metabolic stress

ABSTRACT: Changes in the rate and fidelity of mitochondrial protein synthesis impact the metabolic and physiological roles of mitochondria. Here we explored how environmental stress in the form of a high fat diet modulates mitochondrial translation using mutant mice with error-prone (Mrps12ep/ep) or hyper-accurate (Mrps12ha/ha) mitochondrial ribosomes. We find that while, metabolically both mutations are beneficial in reducing body weight, decreasing circulating insulin and increasing glucose tolerance they cause tissue specific defects when placed on a high fat diet. In contrast to the effect of the mutations on a normal diet the Mrps12ha/ha mice show more pronounced phenotypic and molecular defects as a result of the slow, accurate nature of their protein synthesis. While the Mrps12ep/ep mice accumulate more fat, exhibit larger vacuoles in the liver and lose glucose tolerance, the Mrps12ha/ha mice develop severe hypertrophic cardiomyopathy and hypoxia due to the stress of the diet, showing that benefit or detriment of error-prone and hyper-accurate protein synthesis in mitochondria is dependent on tissue and environmental conditions.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart, Liver

SUBMITTER: Irina Kuznetsova  

LAB HEAD: Aleksandra Filipovska

PROVIDER: PXD021762 | Pride | 2021-09-09

REPOSITORIES: Pride