The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism
Thomas D. Jackson, Daniella H. Hock, Kenji M. Fujihara, Catherine S. Palmer, Ann E. Frazier, Yau Chung Low, Yilin Kang, Ching‐Seng Ang, Nicholas J. Clemons, David R. Thorburn, David A. Stroud, Diana Stojanovski
Abstract
cell lines to understand the effects of AGK dysfunction on mitochondria. This uncovered down-regulation of a number of proteins at the inner mitochondrial membrane, including many SLC25 carrier family proteins, which are predicted substrates of the complex. We also observed down-regulation of SFXN proteins, which contain five transmembrane domains, and show that they represent a novel class of TIM22 complex substrate. Perturbed biogenesis of SFXN proteins in cells lacking AGK reduces the proliferative capabilities of these cells in the absence of exogenous serine, suggesting that dysregulation of one-carbon metabolism is a molecular feature in the biology of Sengers syndrome.