bims-smemid 2026-07-26 papers

Biochim Biophys Acta Mol Cell Res. 2026 Jul 20. pii: S0167-4889(26)00093-5. [Epub ahead of print]1873(7): 120194

Orchestration of OXPHOS biogenesis through regulation of mitochondrial translation.

Andreas Carlström, Carmela Vazquez-Calvo, Martin Ott.

Mitochondrial gene expression is a remnant of the endosymbiotic origin of the organelle, which contains a complete gene expression system that contributes only a handful of subunits to the complexes driving oxidative phosphorylation (OXPHOS). During evolution, many processes of gene expression in mitochondria have diverged from the bacterial ancestor. A central problem to assemble oxidative phosphorylation complexes is that they contain subunits from two genetic sources. Hence, mechanisms have evolved to synchronize expression of nuclear and mitochondrial genes to avoid problems with stoichiometry, which could hamper their assembly. Here, we will summarize recent insights into how gene expression operates with a focus on the mechanisms related to the control of mitochondrial translation in yeast and human cells.

Keywords: Evolution; Gene expression; Mitochondria; Mitoribosomes; Translation initiation; Translational activators; Translational regulation

DOI: https://doi.org/10.1016/j.bbamcr.2026.120194

Mol Cell. 2026 Jul 24. pii: S1097-2765(26)00473-9. [Epub ahead of print]

Distinct sources and effects of mitochondrial reactive oxygen species.

Daniel Barnett, Caroline Booraem, Anna G Orr, Adam L Orr.

Mitochondrial reactive oxygen species (mtROS) have been implicated in aging and disease for decades and are typically viewed as a unitary, non-specific oxidative burden on cells and tissues. However, recent studies have identified at least eleven individual sources of mitochondrial ROS (ISOMRs) and revealed that ISOMRs have distinct, dynamic, and often reversible roles in diverse physiological and pathological processes, including neurodegenerative diseases, immune and metabolic dysregulation, and ischemia-reperfusion injury. This review describes the upstream molecular events that control ISOMR activity, recently developed tools for studying mtROS in general and ISOMRs more specifically, and the evolving perspectives on ISOMR roles in context-specific cell signaling. Future studies to define predictive principles of ISOMR regulation are necessary to open frontiers of redox biology and identify therapeutic strategies for selective modulation of ISOMR-dependent mechanisms in aging and disease.

Keywords: cell metabolism; cell signaling pathways; complex I; complex III; disease mechanisms; electron leak; mitochondria; reactive oxygen species

DOI: https://doi.org/10.1016/j.molcel.2026.07.009

Circ J. 2026 Jul 17.

Altered Plasma Urea Cycle Metabolites Are Independently Associated With Frailty in Patients With Heart Failure.

Katsuhiko Ohori, Toshiyuki Yano, Satoshi Katano, Hidemichi Kouzu, Ryohei Nagaoka, Ryo Numazawa, Kotaro Yamano, Suguru Honma, Aki Habaguchi, Takefumi Fujito, Nobutaka Nagano, Yasunori Umemoto, Masato Furuhashi.

BACKGROUND: Frailty is common in patients with heart failure and is associated with adverse outcomes. Although metabolic dysregulation has been implicated in frailty, the relationship between plasma amino acid profiles and frailty remains incompletely defined.
METHODS AND RESULTS: We conducted a single-center ambispective cross-sectional study of 413 patients hospitalized for heart failure (median age 78 years). Plasma concentrations of 31 amino acids were measured. Frailty status was assessed using the Japanese version of the Cardiovascular Health Study criteria. An unbiased analytical framework integrating multivariate analyses and multivariable logistic regression was applied with adjustment for heart failure severity, renal function, nutritional status, and body composition. Associations with all-cause mortality were evaluated using Cox models. Frailty was present in 228 (55%) patients. Unbiased analyses identified urea cycle-related metabolites as key features associated with frailty. In fully adjusted models, higher plasma citrulline and ornithine concentrations were independently associated with frailty, whereas arginine concentrations were not. These associations were independent of nutritional indices, skeletal muscle mass, and established prognostic factors. Neither citrulline nor ornithine was independently associated with mortality. Pathway analysis demonstrated enrichment of arginine biosynthesis and arginine-proline metabolism.
CONCLUSIONS: Elevated citrulline and ornithine were independently associated with frailty in patients with heart failure, suggesting that dysregulated arginine-related metabolism may represent a metabolic signature of the frailty phenotype distinct from mortality risk.

Keywords: Citrulline; Frailty; Heart failure; Metabolism; Ornithine

DOI: https://doi.org/10.1253/circj.CJ-26-0329