Proteolipid domains form in biomimetic and cardiac mitochondrial vesicles and are regulated by cardiolipin concentration but not monolyso-cardiolipin.

The Journal of Biological Chemistry
Edward Ross PenningtonSaame Raza Shaikh

Abstract

Cardiolipin (CL) is an anionic phospholipid mainly located in the inner mitochondrial membrane, where it helps regulate bioenergetics, membrane structure, and apoptosis. Localized, phase-segregated domains of CL are hypothesized to control mitochondrial inner membrane organization. However, the existence and underlying mechanisms regulating these mitochondrial domains are unclear. Here, we first isolated detergent-resistant cardiac mitochondrial membranes that have been reported to be CL-enriched domains. Experiments with different detergents yielded only nonspecific solubilization of mitochondrial phospholipids, suggesting that CL domains are not recoverable with detergents. Next, domain formation was investigated in biomimetic giant unilamellar vesicles (GUVs) and newly synthesized giant mitochondrial vesicles (GMVs) from mouse hearts. Confocal fluorescent imaging revealed that introduction of cytochrome c into membranes promotes macroscopic proteolipid domain formation associated with membrane morphological changes in both GUVs and GMVs. Domain organization was also investigated after lowering tetralinoleoyl-CL concentration and substitution with monolyso-CL, two common modifications observed in cardiac pathologies. Loss of ...Continue Reading

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Citations

Jul 20, 2019·Journal of Neuroendocrinology·Estefania Acaz-FonsecaMariana Astiz
Sep 20, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·David SchädeliPeter Bütikofer
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Feb 28, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Mohammed El-HafidiCecilia Zazueta
Aug 14, 2021·Cellular and Molecular Life Sciences : CMLS·Magdalena Kulma, Gregor Anderluh

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