bims-cytox1 2026-09-27 papers

Antioxidants (Basel). 2026 Sep 10. pii: 1147. [Epub ahead of print]15(9):

Cunermuspir, a Copper(I)-Niacin Complex, Modulates Mitochondrial Respiration and Cellular Oxidant Handling in Fibroblasts from Children with Autism Spectrum Disorder.

Sophie Wallace, Spencer Lawes, Adrienne C Scheck, Richard E Frye.

Copper is a redox-active transition metal that is essential for the assembly and catalytic function of cytochrome c oxidase (Complex IV), the terminal enzyme of the mitochondrial electron transport chain and a principal site of physiological oxygen reduction. Elevated Complex IV activity and respiratory chain uncoupling are among the most consistently replicated biological findings in autism spectrum disorder (ASD), yet the interaction between mitochondrial copper delivery, respiration, and cellular oxidant handling in ASD has not been systematically defined. We treated dermal fibroblasts from 9 children with ASD and 10 typically developing controls with the copper(I)-niacin complex Cunermuspir (0, 50, or 100 µM for 1 or 24 h exposure) and challenged them with graded concentrations (0-5.0 µM) of the redox-cycling agent 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). Mitochondrial respiration was profiled by Seahorse XF respirometry (2133 observations across 28 experiments), and cellular reactive oxygen species (CellROX™ Green) and mitochondrial mass/polarization (MitoTracker™ Deep Red) were quantified by fluorescence imaging. ASD fibroblasts displayed a hypermetabolic, uncoupled respiratory phenotype (~73% higher baseline respiration; ~109% higher proton leak; reduced coupling efficiency). Linear mixed models with polynomial dose terms revealed significant ASD × Cunermuspir complex interactions (ASD × Cunermuspir and/or their higher-order interactions with DMNQ and treatment) for four respiratory parameters. ASD cells exhibited lower steady-state oxidation-dependent CellROX™ Green fluorescence than controls despite greater respiratory uncoupling, as well as lower steady-state MitoTracker™ Deep Red fluorescence; Cunermuspir reshaped the MitoTracker™ DMNQ dose-response in an ASD-selective manner. These findings identify the Cunermuspir-associated modulation of the ASD mitochondrial and oxidant handling phenotype and motivate further mechanistic and translational evaluation.

Keywords: Complex IV; Cunermuspir; autism spectrum disorder; copper; cuproenzyme; cytochrome c oxidase; mitochondrial respiration; proton leak; reactive oxygen species; redox modulation

DOI: https://doi.org/10.3390/antiox15091147

Nat Commun. 2026 Aug 25. pii: 10162. [Epub ahead of print]17(1):

The predicted interactome of the human mitochondrial proteome.

Abhinav B Swaminathan, Mohammad Zulkifli, Rachel M Guerra, Sofia M Calabrese, Dimitris T Kalafatis, David J Pagliarini, Vishal M Gohil.

Despite the fundamental importance of mitochondria in cellular metabolism, the molecular function(s) of many mitochondrial proteins remain unknown. Since protein function can be inferred from their interacting partners, we repurpose the protein structure prediction algorithm AlphaFold Multimer (AFM) as a classification model to predict protein-protein interactions of the entire human mitochondrial proteome. By screening 630,003 protein pairs, we create a compendium of 2,895 previously known and newly observed interactions, which include the interacting partner(s) of 85 uncharacterized mitochondrial proteins, thereby linking them to a known biochemical pathway. Extending the AFM-based analysis to 11 diverse eukaryotes identifies evolutionarily conserved interactions among human hits, including regulators of core bioenergetic pathways. Our experiments, guided by these predictions, nominate protein interactions that form the coenzyme Q metabolon and define the mitochondrial copper delivery pathway to cytochrome c oxidase. Our compendium represents a powerful resource for the systematic, structure-based functionalization of the human mitochondrial proteome.

DOI: https://doi.org/10.1038/s41467-026-77112-z

Mol Plant. 2026 Sep 23. pii: S1674-2052(26)00312-6. [Epub ahead of print]

A non-canonical DWARF3-OsCOX11-mediated mitochondrial ROS homeostasis pathway acts in parallel with core strigolactone signaling to promote rice blast resistance.

Weijun Cui, Xuming Wang, Xiuli Liu, Hongjia Liu, Yuwen Lu, Fei Yan, Keke Yi, Jianping Chen, Jie Zhou.

Strigolactones (SLs) are a class of plant hormones with multifaceted roles in rice (Oryza sativa L.) growth and development. The F-box protein DWARF3 (D3) is a core component of the SL signalling pathway, coupling SL perception to the downstream responses. However, whether D3 also contributes to rice immunity and how it functions in this process remain unclear. Here, we analysed D3 allelic mutants carrying deletions in F-box- or C-terminal helix (CTH) domains. These mutants exhibited increased susceptibility to Magnaporthe oryzae, and differentially affected the expression of PHENYLALANINE AMMONIA LYASE genes and lignin accumulation, indicating that this canonical SL-regulated pathway contributes to, but does not fully account for, D3-mediated blast resistance. Yeast two-hybrid screening identified OsCOX11, a cytochrome c oxidase (COX) assembly factor, as a D3-interacting protein. D3 promotes the ubiquitination and degradation of OsCOX11, thereby modulating mitochondrial function and reactive oxygen species (ROS) accumulation during immune responses. Loss of D3 function resulted in increased COX activity, aberrant mitochondrial morphology, and compromised elicitor-induced ROS burst, particularly in the CTH-truncated line. Notably, rac-GR24 activated canonical SL signalling but did not measurably alter the D3-OsCOX11 interaction, OsCOX11 abundance, or COX activity under the tested conditions. Together, our findings identify a D3-OsCOX11 mitochondrial branch that operates in parallel with core D3-DWARF53 signalling and contributes to rice blast resistance.

Keywords: D3; OsCOX11; blast resistance; mitochondrial function; reactive oxygen species; strigolactone

DOI: https://doi.org/10.1016/j.molp.2026.09.012