bims-resufa 2026-03-01 papers

Elife. 2026 Feb 23. pii: RP102104. [Epub ahead of print]13

Protein-induced membrane strain drives supercomplex formation.

Maximilian C Pöverlein, Alexander Jussupow, Hyunho Kim, Ville R I Kaila.

Mitochondrial membranes harbor the electron transport chain (ETC) that powers oxidative phosphorylation (OXPHOS) and drives the synthesis of ATP. Yet, under physiological conditions, the OXPHOS proteins operate as higher-order supercomplex (SC) assemblies, although their functional role remains poorly understood and much debated. By combining large-scale atomistic and coarse-grained molecular simulations with analysis of cryo-electron microscopic data and statistical as well as kinetic models, we show here that the formation of the mammalian I/III2 supercomplex reduces the molecular strain of inner mitochondrial membranes by altering the local membrane thickness and leading to an accumulation of both cardiolipin and quinone around specific regions of the SC. We find that the SC assembly also affects the global motion of the individual ETC proteins with possible functional consequences. On a general level, our findings suggest that molecular crowding and strain effects provide a thermodynamic driving force for the SC formation, with a possible flux enhancement in crowded biological membranes under constrained respiratory conditions.

Keywords: bioenergetics; molecular biophysics; molecular dynamics; protein–membrane interactions; respiratory complexes; structural biology; supercomplexes

DOI: https://doi.org/10.7554/eLife.102104

Antioxidants (Basel). 2026 Feb 13. pii: 248. [Epub ahead of print]15(2):

Integrative Proteomic and Bioenergetic Profiling Reveals Diet- and Strain-Specific Mitochondrial Dysfunction in Cohen Diabetic Rat Hearts.

Lauren Pavelich, Tasnim Arroum, Lucynda Pham, Dragana Komnenov, Paul M Stemmer, Rachel Lax, Ann Saada, Sarah Weksler-Zangen, Maik Hüttemann.

Mitochondrial dysfunction contributes to diabetic cardiomyopathy, yet how genetic predisposition and diet interact to reshape cardiac metabolism in diabetic and prediabetic states remains unclear. The Cohen diabetic rat model, comprising diabetes-resistant (CDr) and diabetes-sensitive (CDs) strains, provides a unique platform to dissect this interplay. Here, we present an integrative global proteomic and bioenergetic characterization of cardiac tissue from CDr and CDs rats fed either a regular or a diabetogenic diet. Proteomic pathway mapping revealed downregulation of cytochrome c oxidase (CcO) subunits, strain-dependent rewiring of fatty-acid oxidation pathways, and CcO subunits switch from "heart-type" to "liver-type" isoforms in the sensitive strain. These changes were accompanied by impaired mitochondrial respiration, ATP depletion, and disruption of mitochondrial quality-control mechanisms, together with increased accumulation of tyrosine 304 phosphorylation of cytochrome c oxidase subunit I, indicative of inflammation-driven regulatory inhibition in a diet-specific manner. These findings establish an understanding of how genetic susceptibility and diet contribute to cardiac mitochondrial dysfunction in the Cohen diabetic rat model.

Keywords: CcO6A; CcO7A; cardiomyopathy; cytochrome c oxidase; heart mitochondria; mitochondrial dysfunction; mitochondrial quality control; phosphorylation; proteomic characterization; regulation; respiration; supercomplexes; type 2 diabetes; tyrosine 304 phosphorylation

DOI: https://doi.org/10.3390/antiox15020248

Biomolecules. 2026 Jan 29. pii: 210. [Epub ahead of print]16(2):

Correction: Pavelich et al. Supercomplex Restructuring in Heart Mitochondria of COX7A1-Deficient Mice. Biomolecules 2025, 15, 1209.

Lauren Pavelich, Lucynda Pham, Paul Stemmer, Icksoo Lee, Lawrence I Grossman, Maik Hüttemann, Tasnim Arroum.

In the original publication [...].

DOI: https://doi.org/10.3390/biom16020210