FAM210A is essential for cold-induced mitochondrial remodeling in brown adipocytes

Authors

Jiamin Qiu, Purdue UniversityFollow
Feng Yue, Purdue UniversityFollow
Peipei Zhu, Purdue University
Jingjuan Chen, Purdue UniversityFollow
Fan Xu, Purdue UniversityFollow
Lijia Zhang, Purdue UniversityFollow
Kun Ho Kim, Purdue UniversityFollow
Madigan M. Snyder, Purdue UniversityFollow
Nanjian Luo, Purdue UniversityFollow
Hao-wei Xu, Purdue University
Fang Huang, Purdue UniversityFollow
W. Andy Tao, Purdue UniversityFollow
Shihuan Kuang, Purdue UniversityFollow

Recommended Citation

Qiu, Jiamin; Yue, Feng; Zhu, Peipei; Chen, Jingjuan; Xu, Fan; Zhang, Lijia; Kim, Kun Ho; Snyder, Madigan M.; Luo, Nanjian; Xu, Hao-wei; Huang, Fang; Tao, W. Andy; and Kuang, Shihuan, "FAM210A is essential for cold-induced mitochondrial remodeling in brown adipocytes" (2023). Purdue University Libraries Open Access Publishing Fund. Paper 172.
http://dx.doi.org/10.1038/s41467-023-41988-y

DOI

10.1038/s41467-023-41988-y

Date of this Version

10-10-2023

Abstract

Cold stimulation dynamically remodels mitochondria in brown adipose tissue (BAT) to facilitate non-shivering thermogenesis in mammals, but what regulates mitochondrial plasticity is poorly understood. Comparing mitochondrial proteomes in response to cold revealed FAM210A as a cold-inducible mitochondrial inner membrane protein. An adipocyte-specific constitutive knockout of Fam210a (Fam210aAKO) disrupts mitochondrial cristae structure and diminishes the thermogenic activity of BAT, rendering the Fam210aAKO mice vulnerable to lethal hypothermia under acute cold exposure. Induced knockout of Fam210a in adult adipocytes (Fam210aiAKO) does not affect steady-state mitochondrial structure under thermoneutrality, but impairs cold-induced mitochondrial remodeling, leading to progressive loss of cristae and reduction of mitochondrial density. Proteomics reveals an association between FAM210A and OPA1, whose cleavage governs cristae dynamics and mitochondrial remodeling. Mechanistically, FAM210A interacts with mitochondrial protease YME1L and modulates its activity toward OMA1 and OPA1 cleavage. These data establish FAM210A as a key regulator of mitochondrial cristae remodeling in BAT and shed light on the mechanism underlying mitochondrial plasticity in response to cold.

Comments

This is the publisher PDF of Qiu, J., Yue, F., Zhu, P. et al. FAM210A is essential for cold-induced mitochondrial remodeling in brown adipocytes. Nature Commununications 14, 6344 (2023). This article is distributed under a CC-BY license, and is available at DOI: 10.1038/s41467-023-41988-y.