bims-resufa 2026-11-01 papers

Ann N Y Acad Sci. 2026 Nov;pii: e70440. [Epub ahead of print]1565(1):

Respirasome Persistence Without Efficient Electron Channeling in Cardiac Mitochondria From an Animal Model of Hypertension.

Patrycja Anna Glogowski, Cristina Algieri, Antonia Cugliari, Maria Cotugno, Fabiana Trombetti, Micaela Fabbri, Arrigo Francesco Giuseppe Cicero, Speranza Rubattu, Salvatore Nesci.

Cardiac mitochondrial dysfunction contributes to hypertensive remodeling, but whether respiratory supercomplex organization preserves electron transfer efficiency during disease progression remains unresolved. Here, we examined the structural and functional organization of the respiratory complexes in cardiac mitochondria from stroke-resistant and stroke-prone spontaneously hypertensive rats exposed to normal or Japanese diet regimens. In both models, supramolecular analyses revealed the persistence of N-respirasome and Q-respirasome assemblies, indicating that major respiratory supercomplex species are maintained during sustained hypertension and in the pre-stroke state. However, metabolic flux control analysis consistently showed that cytochrome c oxidase or Complex IV exerted only limited control over respiratory flux, with control coefficients below those expected for tightly channeled nicotinamide adenine dinucleotide (NADH)-dependent electron transfer. Thus, structural preservation of respirasomes was not matched by evidence of kinetically optimized coupling. These findings uncouple supercomplex detectability from functional electron channeling and suggest that, in the hypertensive heart, respiratory performance is constrained by qualitative defects in supercomplex organization rather than by their overt loss.

Keywords: cardiac mitochondria; cytochrome c oxidase; electron flux control; respiratory supercomplexes; spontaneously hypertensive rats

DOI: https://doi.org/10.1111/nyas.70440

Biology (Basel). 2026 Oct 13. pii: 1826. [Epub ahead of print]15(20):

Saponin-Mediated Isolation of Megacomplexes of the Mitochondrial Oxidative Phosphorylation System.

Cunyu Peng, Peixia Hu, Guolin Li, Meichi Wang, Zhigui Duan.

The assembly of mitochondrial oxidative phosphorylation (OXPHOS) supercomplexes determines electron flux and ATP synthesis. Although several techniques have been developed to isolate these supercomplexes, their native assembly states within the inner mitochondrial membrane have remained unclear. Here, we developed a separation technique based on saponins from Sapindus saponaria pericarps that enables the isolation of megacomplexes from mitochondria. Using size-exclusion chromatography (SEC) coupled with Western blot, we found that these megacomplexes may represent the predominant assembly state of the mitochondrial OXPHOS system. Furthermore, co-immunoprecipitation followed by Western blot assays revealed a megacomplex comprising respiratory chain complexes I-IV and ATP synthase. Notably, these supercomplexes remained intact under both fasting and a 24-h high-fat diet, underscoring their stability in vitro. Collectively, this study defines the primary architectural organization of OXPHOS system and establishes the saponin-based method as a mild alternative for extracting membrane protein supercomplexes.

Keywords: Sapindus saponaria saponins; co-immunoprecipitation; mass spectrometry; oxidative phosphorylation supercomplex; size exclusion chromatography

DOI: https://doi.org/10.3390/biology15201826

Antioxidants (Basel). 2026 Oct 21. pii: 1366. [Epub ahead of print]15(10):

BKCa Channel Activation Increases Mitochondrial Supercomplexes and Improves Cardiac Recovery in a Large Animal Model of Myocardial Stunning Following Cardioplegic Arrest and Cardiopulmonary Bypass.

Wenzhuo Ma, Joseph Owusu-Sarfo, Zhiqi Zhang, Scarlett M Silvia, Brenda Cordeiro, Lauren F Bazinet, Thomas Mancini, Benison C Aguocha, Ahmed Aboulgheit, Jin O-Uchi, Bong Sook Jhun, Afshin Ehsan, Gaurav Choudhary, Frank W Sellke, Jun Feng, Martin Kolodziejczack, Dmitry Terentyev, Neel R Sodha, Richard T Clements.

Cardiac surgery or transplant using cardioplegic arrest and cardiopulmonary bypass (CP/CPB) subjects the heart to mild reversible ischemic injury that results in pronounced myocardial stunning. Mitochondrial large conductance calcium-activated K+ channels (BKCa) in cardiomyocytes are potently cardioprotective and beneficially modulate respiration and ROS post-I/R injury. However, how BKCa-dependent K+ flux regulates ROS and respiration is unclear. We evaluated the BKCa activator rottlerin in a preclinical large animal pig CP/CPB model of myocardial stunning and evaluated BKCa-dependent cardioprotective mechanisms in vitro and in vivo. BKCa activation with the small molecule rottlerin significantly improved LV cardiac functional recovery and contractility at 1 h reperfusion. TEM showed larger mitochondria in the rottlerin group consistent with K+ influx. We also found that pigs with rottlerin treatment had increased electron transport chain supercomplexes (mSCs), which are thought to improve respiratory efficiency and reduce ROS. Consistent with increased mSC, rottlerin reduced ROS-dependent protein modification in CP/CPB pigs. In complementary studies, rottlerin and/or adenoviral overexpression of a mutant mito-BKCa increased respiration, altered mitochondrial morphology, increased mSC assembly, and significantly reduced ROS following in vitro CP/reoxygenation, similar to CP/CPB pigs. In summary, mito-BKCa activation increases mSCs and respiration while reducing ROS, suggesting that mSC-dependent improved respiratory efficiency promotes robust cardioprotection.

Keywords: BKCa; Slo1; cardioprotection; ischemia; mallotoxin; potassium; respirasome; supercomplex

DOI: https://doi.org/10.3390/antiox15101366