Translocase of the mitochondrial inner membrane (TIM) is essential for importing nuclear-encoded proteins, a critical process for organelle biogenesis and function. While TIM is well-characterized in a wide range of eukaryotes, it is remarkably divergent in the parasitic protozoan Trypanosoma brucei, the causative agent of human and animal African trypanosomiasis. Unlike the canonical TIM23 and TIM22 complexes found in opisthokonts, T. brucei possesses a single, essential TIM complex built...

Tim17 forms the protein-conducting channel of the mitochondrial inner membrane translocase. Here, authors show that the N-terminus of Tim17 constitutes a negatively charged selectivity filter to facil...

Das et al. show that succinate regulates mitochondrial protein import through an interaction between Sfc1 (succinate-fumarate carrier) and the Tim23 translocase subunit. In the absence of succinate, Sfc1 associates with Tim23 and reduces protein import. Succinate promotes dissociation of the Sfc1-Tim23 complex, thereby enhancing TIM23 mediated protein translocation into mitochondria.

The mitochondrial inner membrane complexes TIM23 and TIM22 mediate distinct protein topogenesis functions in polypeptide import. The authors reveal their mechanistic overlap in topogenic sequence reco...

Read the full paper: Succinate and its carrier Sfc1 mediate metabolic control of mitochondrial protein import by the TIM23 translocase

Nature Structural & Molecular Biology, Published online: 28 August 2025; doi:10.1038/s41594-025-01662-xYang et al. uncover the molecular details of how mitochondrial proteins cross the outer and inner mitochondrial membranes, with hydrophobicity guiding them into distinct pathways toward specific destinations.

Nature Structural & Molecular Biology, Published online: 28 August 2025; doi:10.1038/s41594-025-01662-xYang et al. uncover the molecular details of how mitochondrial proteins cross the outer and inner mitochondrial membranes, with hydrophobicity guiding them into distinct pathways toward specific destinations.

Hsu et al. show that mitochondrial import blockage stress activates the ATP-dependent protease YME1L1, which degrades mitochondrial presequence translocase TIM23 subunits to promote cell growth.

Yang et al. uncover the molecular details of how mitochondrial proteins cross the outer and inner mitochondrial membranes, with hydrophobicity guiding them into distinct pathways toward specific desti...

Hsu et al. show that mitochondrial import blockage stress activates the ATP-dependent protease YME1L1, which degrades mitochondrial presequence translocase TIM23 subunits to promote cell growth.

Yang et al. uncover the molecular details of how mitochondrial proteins cross the outer and inner mitochondrial membranes, with hydrophobicity guiding them into distinct pathways toward specific desti...

TIM23 core deficiency specifically impacts the oxidative phosphorylation and the mitochondrial ribosome complexes and, unexpectedly, leads to reduction of plasma membrane voltage-dependent potassium c...

TIM23 core deficiency specifically impacts the oxidative phosphorylation and the mitochondrial ribosome complexes and, unexpectedly, leads to reduction of plasma membrane voltage-dependent potassium c...

Hsu et al. show that mitochondrial import blockage stress activates the ATP-dependent protease YME1L1, which degrades mitochondrial presequence translocase TIM23 subunits to promote cell growth.