LETMD1 regulates mitochondrial protein synthesis and import to guard brown fat mitochondrial integrity and function.

ABSTRACT: Thermogenic brown adipocytes (BAs) catabolize lipids to generate heat, representing powerful agents against the growing global obesity epidemic. We and others reported recently that LETMD1 is a BA-specific protein essential for mitochondrial structure and function, but the mechanisms of action remain unclear. We performed sequential digestion to demonstrate that LETMD1 is a trans-inner mitochondrial membrane protein. We then generated UCP1Cre-driven BA-specific Letmd1 knockout (Letmd1 ^UKO ) mice to show that Letmd1 ^UKO leads to protein aggregation, reactive oxidative stress, hyperpolarization, and mitophagy in BAs. We further employed TurboID proximity labeling to identify LETMD1-interacting proteins. Many candidate proteins a

SUBMITTER: Snyder M 

PROVIDER: S-EPMC11467678 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature