Nathan Alder and Eric May have been awarded an R01 grant from the NIH National Heart, Lung and Blood Institute (NHLBI) as co-investigators on a project led by Steve Claypool at the Johns Hopkins University School of Medicine. The project, entitled “An intimate and multifaceted partnership: cardiolipin and the mitochondrial ADP/ATP carrier” (R01HL165729), is a four-year award, with a total award amount exceeding $2 million. This project will use multidisciplinary approaches for understanding the functional interactions between the ADP/ATP carrier (AAC) of the mitochondrial inner membrane and cardiolipin, the signature phospholipid of the mitochondrion. Following up on recent research progress from the Claypool group, the work supported by this grant will elucidate how cardiolipin regulates AAC folding as well as higher-order assembly of AAC with the respiratory chain supercomplex, both of which are essential for mitochondrial energy metabolism. The labs at MCB will make complementary contributions to the work, using biophysical techniques with mitochondrial and reductionist model systems (Alder Lab) and computational approaches to address dynamic AAC-lipid interactions (May Lab). A key objective of this research is to elucidate the molecular basis of disease-associated defects in AAC-cardiolipin interactions that may arise from alterations in lipid metabolism and heritable mutations in the AAC transporter. These insights will inform current models of AAC regulation and the role of AAC-lipid interactions in mitochondrial diseases.

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