bims-mitpro 2025-12-28 papers

Issue of 2025–12–28
two papers selected by
Andreas Kohler, Umeå University

Cell Rep. 2025 Dec 18. pii: S2211-1247(25)01499-8. [Epub ahead of print]45(1): 116727

Mitochondrial contact site and cristae organizing system promotes modular assembly of cytochrome c oxidase.

Lilia Colina-Tenorio, Patrick Horten, Enzo Scifo, Susanne E Horvath, Rhena F U Klar, Chantal Priesnitz, Fabian den Brave, Martin van der Laan, Thomas Becker, Kuo Song, Heike Rampelt.

Mitochondrial cytochrome c oxidase, complex IV (CIV) of the respiratory chain, is assembled in a modular fashion from mitochondrial as well as nuclear-encoded subunits, guided by numerous assembly factors. This intricate process is further complicated by the characteristic architecture of the inner mitochondrial membrane. The mitochondrial contact site and cristae organizing system (MICOS) maintains the stability of crista junctions that connect the cristae, the site of mitochondrial respiration, with the inner boundary membrane, where newly imported respiratory subunits first arrive. Here, we report that MICOS facilitates specific assembly steps of CIV and associates with intermediates of the Cox1 and Cox3 modules. Moreover, MICOS recruits a variety of assembly factors even in the absence of ongoing CIV biogenesis, directly or via the mitochondrial multifunctional assembly (MIMAS). Our results establish MICOS as an important agent in efficient respiratory chain assembly that promotes CIV biogenesis within the compartmentalized inner membrane architecture.

Keywords: CP: Cell biology; CP: Metabolism; MICOS; MIMAS; Mic60; cristae; cytochrome c oxidase; mitochondria; protein assembly; respiratory chain

DOI: https://doi.org/10.1016/j.celrep.2025.116727

J Proteome Res. 2025 Dec 22.

Proximity Labeling Reveals RNA-Binding Proteins Associating with the Human Mitochondrial Import Receptor TOMM20.

Saira Akram, Katharina I Zittlau, Karan Sharma, Julia C Fitzgerald, Nisha Rafiq, Boris Maček, Ralf-Peter Jansen.

The import of most mitochondrial proteins requires that their precursor proteins be bound by the peripheral receptor proteins TOM20, TOM22, and TOM70. Budding yeast TOM20 and TOM70 have been extensively studied regarding their interaction partners and recognized substrates; however, little data is available for metazoan cells. Using APEX2-based proximity labeling, we created association profiles for human TOMM20 and TOMM70 in HeLa cells. We focused particularly on their interactions with RNA-binding proteins (RBPs) because there is evidence of RNA association with the mitochondrial outer membrane (MOM) and of local translation at the mitochondrial surface, however, these processes are poorly understood. Our results demonstrate that several RBPs and translation factors preferentially associate with TOMM20 rather than TOMM70. These include SYNJ2BP, a previously identified membrane-bound RBP that binds and protects mRNA encoding mitochondrial proteins. Inhibiting translation with puromycin increased the association of these RBPs with TOMM20 compared to TOMM70. This suggests that TOMM20, but not TOMM70, may play a role in maintaining cellular homeostasis during translation stress by retaining protective RBPs and translation-related proteins at the MOM.

Keywords: APEX2; SYNJ2BP; TOMM20; TOMM70; mitochondrial import; proteomics; proximity labeling

DOI: https://doi.org/10.1021/acs.jproteome.5c00905