bims-mitpro 2025-07-27 papers

Issue of 2025–07–27
two papers selected by
Andreas Kohler, Umeå University

J Biol Chem. 2025 Jul 16. pii: S0021-9258(25)02333-6. [Epub ahead of print] 110483

Stressful situations: molecular insights on mitochondrial quality control pathways.

Sabrina Romanelli, Jean-François Trempe.

Mitochondrial quality control has emerged as an important area of research over the past decade, with more than 2,000 publications exploring the molecular pathways that regulate it. Mitochondria are essential for energy production and various cellular functions but are highly susceptible to damage from stressors such as protein misfolding, reactive oxygen species, and chemicals that disrupt the electron transport chain. If left unresolved, mitochondrial dysfunction can lead to health complications, including neurodegenerative disorders, cardiovascular diseases, and cancer. To maintain cellular health, cells evolved quality control pathways to remove damaged mitochondrial components. This review focuses on three key quality control responses: the PINK1-Parkin pathway, the DELE1-HRI pathway, and the mitochondrial unfolded protein response (UPRmt). While these pathways have distinct functions, there is ongoing debate about how they overlap and which responds first in different contexts. In this review, we discuss the physiological and structural mechanisms behind each pathway, explore how they interconnect, and highlight their differences and relevance to disease. By summarizing this information in a single review, we aim to enhance the molecular understanding of mitochondrial quality control, which can help highlight avenues for novel therapeutics for diseases associated to dysfunctional mitochondria.

DOI: https://doi.org/10.1016/j.jbc.2025.110483

J Cell Sci. 2025 Jul 24. pii: jcs.263736. [Epub ahead of print]

The mammalian protein MTCH1 can function as an insertase.

Anna Roza Dimogkioka, Anni Elias, Doron Rapaport.

The outer mitochondrial membrane (OMM) hosts a variety of proteins such as import machineries, enzymes, fission/fusion factors, and pore proteins. In Saccharomyces cerevisiae, the MIM complex, consisting of Mim1 and Mim2, mediates the insertion of α-helical proteins into the OMM. Until recently, it was unclear which proteins serve this function in higher eukaryotes. Recent studies identified MTCH2 as the insertase of α-helical proteins into the OMM in mammals. MTCH1 is a paralogue of MTCH2 but its general function and contribution to the biogenesis process are not clear. To better characterize MTCH1, we explored whether MTCH1 or MTCH2 could functionally replace Mim1/Mim2 in yeast. Expression of MTCH1 and MTCH2 in yeast cells lacking Mim1, Mim2, or both revealed that MTCH1, but not MTCH2, could compensate the growth defects upon deleting the MIM complex. Furthermore, MTCH1 could restore the biogenesis of MIM substrates, TOM complex stability, and morphology of mitochondria. These findings indicate that MTCH1 by itself has insertase activity and is a functional homologue of the MIM complex, despite the absence of any evolutionary relation between the mammalian and yeast insertases.

Keywords: Insertase; MIM; MTCH1; MTCH2; Mitochondria; Outer membrane

DOI: https://doi.org/10.1242/jcs.263736