An essential requirement of cardiolipin for mitochondrial carnitine acylcarnitine translocase activity

Abstract

The phospholipid requirement for the optimal solubilization of carnitine acylcarnitine translocase from the inner membrane vesicles of rat liver mitochondria and for its reconstitution in liposomes was investigated. At the octylglucoside-solubilization step, the presence of cardiolipin proved superior to the other lipids tested. For reconstitution, a mixture having phosphatidylcholine, phosphatidylethanolamine and cardiolipin was found to be particularly effective. The requirement of cardiolipin at this step was met less effectively by other anionic phospholipids. Moreover, in intact mitochondria of rat liver and heart, the translocase activity was markedly inhibited by micromolar concentrations of doxorubicin, a specific cardiolipin-binding agent.Carnitine acylcarnitine translocase, involved in the transmitochondrial transport of carnitine and its esters, has been solubilized from inner membrane vesicles of rat liver mitochondria with octyl glucoside and reconstituted into asolectin liposomes using the octyl glucoside dilution method [l]. Continuing studies on the optimization of these procedures have revealed an esstential requirement of cardiolipin for the translocase activity. These are being described herein.

NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy

“…Many IMM proteins have CL-binding domains, thus limiting free exchange and redistribution of the phospholipid to the OMM. [28][29][30][31][32][33][34][35][36] In some of these proteins, CL molecules are buried 'deeply' within multimeric protein complexes (like in electron-transporting respirasomes 35,36 ), whereas in the others the affinity and accessibility of CL for translocations seem to be less restricted (e.g., TIM40 37 ). Although the exact amounts of CL in the two pools -free versus bound -have not been established, it is likely that in normally functioning mitochondria, the majority of the IMM CLs is not readily mobilized.…”

Myocardial Regulation of Lipidomic Flux by Cardiolipin Synthase

“…In addition, CL modulates adenine nucleotide translocase activity (6,7), supercomplex formation (8,9), acyl carnitine carrier activity (10), mitochondrial fission and fusion (11), phosphate carrier and pyruvate transporter activities (12), ␣-ketoglutarate dehydrogenase activities (13), and apoptosis (14 -16). Understanding the chemical mechanisms underlying the multiple diverse functions of CL in mitochondrial bioenergetics and signaling will ultimately require the integration of genetic, lipidomic, and pharmacologic approaches to determine the interwoven relationships between CL content and molecular species composition with the pleiotropic roles of mitochondria in health and disease.…”

Isolation of a Chinese Hamster Ovary (CHO) cDNA Encoding Phosphatidylglycerophosphate (PGP) Synthase, Expression of Which Corrects the Mitochondrial Abnormalities of a PGP Synthase-defective Mutant of CHO-K1 Cells

“…CL represents from 0.2 to 15% of total lipid phosphorous in various animal tissues and is located primarily in the inner mitochondrial membrane (1). Biochemical analysis suggests that CL is required for many enzymatic activities, such as cytochrome c oxidase (5) and carnitine acylcarnitine translocase (6), and is involved in cellular functions, such as mitochondrial protein import (7)(8)(9)(10) and binding of matrix Ca 2ϩ (11). In yeast cells, most of the requirement for CL for mitochondrial functions appears to be substituted by an increase in PG content (12).…”