bims-cytox1 2026-02-15 papers

Proc Natl Acad Sci U S A. 2026 Feb 17. 123(7): e2524884123

A photosynthetic-respiratory electron transport chain chimera based on photosystem I and cytochrome c oxidase on graphene oxide.

Xiaoping Zhu, Matthew J Kummer, Carolyn E Lubner, Vasily Kurashov, William Carr, John H Golbeck, Robert A Niederman, Lev G Mourokh, Shelley D Minteer, Paul G Falkowski, Michele Vittadello.

The self-assembly of enzyme proteins on 2D nanomaterials has enabled the construction and functional control of viable biochemical pathways. However, enzymatic cascades, which combine essential components of the photosynthetic and respiratory electron transport chains in tandem, have thus-far remained elusive. Herein, we have investigated a galvanic biohybrid nanosystem coupling photosystem I and cytochrome c oxidase on the surface of graphene oxide nanosheets in colloidal suspension. The oriented immobilization of the enzymes was facilitated by Ni-coordination sites tethered to the carbon basal plane, with negligible parasitic O2 consumption. Transient absorption and electrochemical measurements provided evidence of electron transfer between donors and acceptors, leading to light-induced O2 consumption of up to 70 out of 120 O2 molecules/s/CcO unit. Graphene oxide behaves as an electronic reservoir and as an electroactive support, enabling electron transport, in concert with cytochrome c, as well as small-molecule redox mediators and reductants. This study provides a state-of-the-art approach for the exploration of photoelectron transfer in membrane-free suspensions of nanosurface-anchored photosynthetic-respiratory enzymatic chains.

Keywords: cytochrome c oxidase; electron transfer; graphene oxide; oxygen-reduction reaction; photosystem I

DOI: https://doi.org/10.1073/pnas.2524884123

Mol Genet Metab. 2026 Feb 08. pii: S1096-7192(26)00050-8. [Epub ahead of print]147(3): 109767

Rhabdomyolysis due to mtDNA pathogenic variants: Report of a subject with a novel MT-CO3 variant and review of the literature.

Emanuele Barca, Nuri Jacoby, Ali Naini, Michael L Miller, Valentina Emmanuele, Christopher J Winfree, Saba Tadesse, Kurenai Tanji, Michio Hirano.

Rhabdomyolysis can be due to mitochondrial myopathy, but mitochondrial DNA (mtDNA) pathogenic variants are often overlooked in standard genetic panels. We report a 41-year-old woman with recurrent rhabdomyolysis due to a novel MT-CO3 variant. Muscle biopsy showed cytochrome c oxidase-negative fibers that segregated with high heteroplasmic load on single-fiber. We additionally review previously reported mtDNA variants associated with rhabdomyolysis, highlighting the diagnostic relevance of mtDNA analysis and tissue-specific testing in unexplained rhabdomyolysis.

Keywords: COX stain; Mitochondrial DNA; Rhabdomyolysis; Single-fiber analysis; mtDNA pathogenic variant

DOI: https://doi.org/10.1016/j.ymgme.2026.109767

J Genet Genomics. 2026 Feb 08. pii: S1673-8527(26)00047-0. [Epub ahead of print]

Optic neuropathy arising from the synergy between YARS2 and mitochondrial COX1 mutations.

Huiying Li, Cheng Ai, Xiaofen Jin, Jing Wang, Jun Yu, Yinlong Gao, Douglas C Wallace, Min-Xin Guan.

Leber hereditary optic neuropathy (LHON) is a paradigm for mitochondrial retinopathy. Here, we investigate the mechanism underlying the interaction between nuclear modifier and mtDNA mutation(s) that manifests optic neuropathy in vivo to develop an effective therapeutic approach for this disease using mouse models bearing LHON-linked Yars2G186V or COIV421A mutation alone and double mutations. Yars2G186V alters mitochondrial translation and assembly and activities of complex I, III, and IV, while COIV421A reduces complex IV activity. However, a single Yars2G186V or COIV421A mutation causes mild declines in ATP production and yields relatively mild degeneration of retinal ganglion cells (RGCs). Notably, the synergy between COIV421A and Yars2G186V mutations aggravates mitochondrial dysfunction and oxidative stress. Interestingly, COIV421A mainly promotes apoptosis, and Yars2G186V contributes to ferroptosis. The combination of two mutations accelerates the degeneration of RGCs and photoreceptors. Strikingly, AAV-mediated Yars2 expression in the mouse retina carrying both Yars2G186V and COIV421A mutations corrects the defective translation and ferroptosis arising from the Yars2G186V mutation and remarkably improves mitochondrial function and causes morphologic and functional recovery of RGCs and photoreceptors. These findings provide mechanistic insights into the pathophysiology of LHON arising from nuclear modifiers and mtDNA mutation(s) and potential therapeutic strategies for LHON and other mitochondrial diseases.

Keywords: Apoptosis; Ferroptosis; Gene therapy; Mitochondrial DNA mutation; Mitochondrial tyrosyl-tRNA synthetase; Optic neuropathy; Oxidative phosphorylation

DOI: https://doi.org/10.1016/j.jgg.2026.02.003