The architecture of substrate-engaged TOM–TIM23 supercomplex reveals preprotein proximity sites for mitochondrial protein translocation
Qiang Wang, Jinjin Zhuang, Rui Huang, Zeyuan Guan, Ling Yan, Sixing Hong, Liying Zhang, Can Huang, Zhu Liu, Ping Yin
Abstract
Mitochondria, housing at least 1000 proteins, play a pivotal role as an organelle, facilitating energy production and metabolite synthesis 1 , 2 . Mitochondrial proteins are primarily synthesized within the cytosolic ribosome and subsequently transferred to specific mitochondrial compartments through the corresponding translocase complexes, including the translocase of the outer mitochondrial membrane (TOM) and the translocase of the inner mitochondrial membrane (TIM23) 3 . As the main entry gate of mitochondria, the TOM complex is responsible for transferring ~90% of mitochondrial proteins from the cytosol into the mitochondria 1 , 4 . These mitochondrial proteins are known as preproteins before entering mitochondria. The mitochondrial matrix proteins are the most abundant protein type within mitochondria, and these proteins with N-terminal presequence are transferred into mitochondria successively by both the TOM and TIM23 complexes 1 , 3 . The TOM and TIM23 complexes are assembled into a transient supercomplex, thus promoting the translocation of preproteins 5 . Although the assembly of the TOM and TIM23 complexes has been elucidated 6 , 7 , 8 , 9 , respectively, little is known about how presequence-carrying preproteins pass through the TOM complex.