Saltar al contenido
Merck

SARS-CoV-2 infection enhances mitochondrial PTP complex activity to perturb cardiac energetics.

iScience (2022-01-11)
Karthik Ramachandran, Soumya Maity, Alagar R Muthukumar, Soundarya Kandala, Dhanendra Tomar, Tarek Mohamed Abd El-Aziz, Cristel Allen, Yuyang Sun, Manigandan Venkatesan, Travis R Madaris, Kevin Chiem, Rachel Truitt, Neelanjan Vishnu, Gregory Aune, Allen Anderson, Luis Martinez, Wenli Yang, James D Stockand, Brij B Singh, Subramanya Srikantan, W Brian Reeves, Muniswamy Madesh
RESUMEN

SARS-CoV-2 is a newly identified coronavirus that causes the respiratory disease called coronavirus disease 2019 (COVID-19). With an urgent need for therapeutics, we lack a full understanding of the molecular basis of SARS-CoV-2-induced cellular damage and disease progression. Here, we conducted transcriptomic analysis of human PBMCs, identified significant changes in mitochondrial, ion channel, and protein quality-control gene products. SARS-CoV-2 proteins selectively target cellular organelle compartments, including the endoplasmic reticulum and mitochondria. M-protein, NSP6, ORF3A, ORF9C, and ORF10 bind to mitochondrial PTP complex components cyclophilin D, SPG-7, ANT, ATP synthase, and a previously undescribed CCDC58 (coiled-coil domain containing protein 58). Knockdown of CCDC58 or mPTP blocker cyclosporin A pretreatment enhances mitochondrial Ca2+ retention capacity and bioenergetics. SARS-CoV-2 infection exacerbates cardiomyocyte autophagy and promotes cell death that was suppressed by cyclosporin A treatment. Our findings reveal that SARS-CoV-2 viral proteins suppress cardiomyocyte mitochondrial function that disrupts cardiomyocyte Ca2+ cycling and cell viability.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
ANTI-FLAG® M2 monoclonal antibody produced in mouse, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Sigma-Aldrich
Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, ≥98% (TLC), powder
Sigma-Aldrich
Nifedipine, ≥98% (HPLC), powder
Millipore
FLAG® HA Tandem Affinity Purification Kit