bims-mitran 2025-11-23 papers

Issue of 2025–11–23
two papers selected by
Andreas Kohler, Umeå University

Mitochondrion. 2025 Nov 16. pii: S1567-7249(25)00096-0. [Epub ahead of print] 102099

The mitochondrial protein TMEM177 fine-tunes mammalian cytochrome c oxidase assembly.

Jakob D Busch, Thomas Schöndorf, Dusanka Milenkovic, Xinping Li, Rolf Wibom, Joana F Silva-Rodrigues, Roberta Filograna, Camilla Koolmeister, Nils-Göran Larsson, Diana Rubalcava-Gracia.

The mitochondrial cytochrome c oxidase (COX, complex IV), a multi-subunit protein complex, plays a crucial role in cellular respiration by reducing oxygen to water and simultaneously pumping protons to enable oxidative phosphorylation (OXPHOS). Thus, defects in its assembly can directly affect cellular energy homeostasis. COX20 is an essential chaperone for the core subunit COX2. In human cultured cells, TMEM177 was found to stabilize COX20 and maintain balanced COX2 levels. In mice, TMEM177 was also identified as an interactor of mitochondrial ribosomes. To understand the function of TMEM177 in vivo, we generated Tmem177 knockout mice. Here, we analyze how TMEM177 loss affects mitochondrial gene expression, as well as the activity and assembly of OXPHOS complexes. We found that a small proportion of the knockout mice died perinatally, while surviving knockout mice tended to gain less weight. TMEM177 depletion moderately reduced COX20 levels, but OXPHOS complexes were preserved. Moreover, Tmem177 and Surf1 double knockout mice were born asymptomatic. In conclusion, TMEM177 fine-tunes complex IV assembly by stabilizing COX20 in vivo. Our findings refine the current model of complex IV assembly in mammals.

Keywords: Cytochrome c oxidase; Mitochondria; Mitoribosomes; OXPHOS; mtDNA

DOI: https://doi.org/10.1016/j.mito.2025.102099

Sci Rep. 2025 Nov 17. 15(1): 40201

Caloric restriction enhances inheritance of wild-type mitochondrial DNA in Saccharomyces cerevisiae.

Wenjuan Zhu, Minoru Yoshida, Feng Ling.

In Saccharomyces cerevisiae, an asymmetrical division model, mitochondrial (mt) DNA typically exists in a homoplasmic state, but mutations frequently occur. Rolling-circle replication, mediated by the mtDNA recombinase Mhr1p, forms tandem concatemers that are selectively transmitted to budding cells. In crosses between haploids with wild-type (ρ+) and hypersuppressive (HS) ρ- mtDNA, ρ- progeny are predominantly produced due to the replicative advantage of mtDNA with large deletions. We investigated the effects of caloric restriction (CR; 0.5% glucose medium) on mitochondrial distribution and found that ρ+ mtDNA-mitochondria are pre-selected in zygotes and transmitted into buds prior to mitochondrial fusion. This process, termed ρ+ mtDNA-mitochondrial preselection and transmission (ρ+ mtDNA-MPT), was validated by confocal imaging and flow cytometry analyses. The rate of ρ+ progeny increased under CR conditions compared to glucose-abundant media, suggesting that CR enhances ρ+ mtDNA-MPT and promotes the formation of wild-type mtDNA homoplasmy via an Mhr1p-dependent mechanism, which dominates mtDNA inheritance.

Keywords: Heteroplasmy; Homoplasmy; Hypersuppresiveness; Mitochondria; Nonmedial budding.; Preselection; mtDNA

DOI: https://doi.org/10.1038/s41598-025-23888-x