bims-mitpro 2026-07-19 papers

Issue of 2026–07–19
two papers selected by
Andreas Kohler, Umeå University

J Mol Biol. 2026 Jul 14. pii: S0022-2836(26)00318-9. [Epub ahead of print] 169945

Distinct Assembly Complexes facilitate cbb3-type Cytochrome Oxidase Maturation.

Kaiwei Shen, Yavuz Öztürk, Jorge Jimenez-Niebla, Philip Dafe Emmanuel, Katharina Ruoff, Miguel Cosenza-Contreras, Friedel Drepper, Pitter Huesgen, Carola Hunte, Fevzi Daldal, Hans-Georg Koch.

Cytochrome oxidase (Cox) assembly is inherently challenging because subunit associations need to be tightly coordinated with cofactor insertions. In mitochondria, this process relies on large assembly machineries, whereas bacterial Cox assembly has been thought to involve mostly only brief interactions between assembly factors and subunits. However, here we identified three stable assembly complexes of 500, 390, and 150 kDa that are required for the maturation of cbb3‑type Cox in the α‑proteobacterium R. capsulatus. These complexes mediate the stepwise insertion of heme and copper cofactors and are organized around the cupric reductase CcoG, which forms together with the ATPase CcoI and the chaperones SenC and CcoS a copper insertion module. Formation and stability of these complexes is determined by copper loading of CcoG and CcoI. Overall, our findings demonstrate that large multi-protein assembly machineries also exist in bacteria and are required for the maturation of cbb3-Cox, the most ancient bacterial Cox.

Keywords: Rhodobacter capsulatus; copper homeostasis; cytochrome oxidase; cytochromes; protein assembly

DOI: https://doi.org/10.1016/j.jmb.2026.169945

Biochim Biophys Acta Mol Cell Res. 2026 Jul 16. pii: S0167-4889(26)00090-X. [Epub ahead of print] 120191

Metformin triggers ATF4-mediated UPRmt and COX-2 inflammation in adipocytes.

Juthakorn Poothong, Chutipong Chiamkunakorn, Wichit Suthammarak, Teva Phanaksri, Prasert Auewarakul, Jing Yong, Randal J Kaufman.

Metformin is the most common drug for type 2 diabetes due to its action to improve insulin sensitivity and enhance glucose uptake in tissues, including adipose tissue. As a mitochondrial complex I inhibitor, treatment with metformin may cause deleterious effects. Here, we demonstrated that treatment of adipocytes 3 T3-L1 cells with a high concentration of metformin (10 mM) led to increased reactive oxygen species (ROS) accumulation and triggered the mitochondrial unfolded protein response (UPRmt), as revealed by increased mRNA expression of UPRmt markers (mtHSP70, Lonp1, and FGF21). High-concentration metformin also induced COX-2 inflammation, as indicated by increased NF-κB phosphorylation and cyclooxygenase-2 (COX-2) expression. By contrast, a lower concentration (1.25 mM) showed no effects. We found that ATF4 was selectively upregulated and was required for UPRmt and COX-2 inflammation induced by metformin. Interestingly, we showed that the integrated stress response inhibitor (ISRIB) effectively inhibited ATF4, mitigated metformin-induced UPRmt, and reduced NF-κB/COX-2 expression. Taken together, our findings point to the undesirable effect of the high-concentration metformin in adipocytes.

Keywords: ATF4; COX-2; ISRIB; Metformin; ROS; UPR(mt)

DOI: https://doi.org/10.1016/j.bbamcr.2026.120191