bims-mitpro 2026-07-26 papers

Issue of 2026–07–26
two papers selected by
Andreas Kohler, Umeå University

Nat Struct Mol Biol. 2026 Jul 23.

Direct coupling of human TOM and TIM22 complexes drives mitochondrial carrier import.

Xiaolong Liu, Hongjun Cai, Hao Wang, Xueyin Zhou, Yutong Zhang, Shuai Liu, Jiajun Zhu, Long Li.

Metabolite carriers that control essential metabolite transport are imported into mitochondria through the TOM and TIM22 complexes. How TOM and TIM22 coordinate in human mitochondria has remained largely unknown. Here we show that human TOM and TIM22 assemble into a supercomplex that seamlessly couples carrier translocation across the outer and inner membranes, unlike in yeast where the two complexes appear to function separately. Cryo-electron microscopy structures of the human TOM-TIM22 supercomplex reveal unpaired carrier transmembrane segments traversing the TOM channel along a hydrophobic path and exiting through an unexpected lateral groove outside the channel. The membrane-bound small Tim subunits provide the substrate entry site for TIM22, while a membrane-exposed groove of TIM22 serves as the exit for carrier insertion into the inner membrane. These findings provide insights into the human carrier translocation pathway at molecular resolution and establish the TOM-TIM22 supercomplex as a central organizing unit of mitochondrial carrier import.

DOI: https://doi.org/10.1038/s41594-026-01849-w

Nat Commun. 2026 Jul 21. pii: 6128. [Epub ahead of print]17(1):

Mitochondrial translation termination, recycling, reinitiation, and rescue for in-frame and out-of-frame contexts.

Taisei Wakigawa, Mari Mito, Qi Fang, Yuzuru Itoh, Yoichi Shinkai, Shintaro Iwasaki.

Because mitochondria diverged from a bacterial ancestor during evolution, the mitochondrial protein synthesis system includes both mRNAs and translation factors with unique characteristics. However, the molecular mechanisms underlying translation termination, recycling, and quality control remain unclear. Here, via high-resolution mitochondrial Ribo-Seq and Disome-Seq, we reveal: the specificity of release factors for different kinds of stop codons; the role of mtRF1 in vertebrates, which do not have noncanonical stop codons in their main translons; the recycling-coupled translation of internal translons; and the rescue of mitoribosomes in the early elongation stage. mtRF1L recognizes all stop codons, whereas mtRF1 recognizes only AGA/AGG noncanonical stop codons. Additionally, mtRF1 terminates the translation of out-of-frame translons that end with AGA/AGG. We also found that mtRRF and mtIF3 are required for mitoribosome recycling on stop codons and for the reinitiation of internal translon translation. Mitoribosomes that stall at the start codons and/or at the early elongation phase are major substrates of the rescue factors ICT1, mtRF-R, and mtRES1. Moreover, HEMK1-mediated methylation of release factors enhances the termination reaction on stop codons. Our results provide insights into the mitoribosome dynamics that are associated with the completion of protein synthesis.

DOI: https://doi.org/10.1038/s41467-026-75248-6