TMEM41B: An Evolutionarily Conserved Nexus in Thermogenic Regulation

ABSTRACT: Thermogenesis is a crucial homeostatic mechanism that has evolved significantly during vertebrate evolution. However, the molecular mechanisms of thermogenic evolution are not well understood. In this study, our phylogenetic analysis highlights a vital role for TMEM41B in thermogenesis. Mice lacking TMEM41B in either skeletal muscle or brown adipocytes, two key organs involved in heat production, exhibit cold intolerance, highlighting the essential role of TMEM41B in thermoregulation. Furthermore, Turbo-ID-MS analysis reveals that TMEM41B is localized at the mitochondrial-associated ER membranes (MAMs), and its deficiency disrupts ER-mitochondria contacts and impairs mitochondrial dynamics. Evolutionary analysis and the rescue experiments shows that the N-terminal region of TMEM41B is critical for its thermogenic function. Overall, this study identifies TMEM41B as a critical evolutionary factor essential for thermogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE287714 | GEO | 2025/05/01

REPOSITORIES: GEO