Hoppel 2017 MiP2017
Hoppel CL (2017)
To examine the state of CPT1a in the mtOM, an approach was used that combined sizing by mass and isolation by immunological methods. Blue native electrophoresis of purified rat liver mtOM extracts yielded several high molecular weight bands containing CPT1a, ACSL, and VDAC; IP of mtOM extracts with CPT1a antibodies or antisera against ACSL and VDAC revealed strong interactions between these 3 proteins. This strongly suggests that CPT1a forms hetero-oligomeric complexes with ACSL and VDAC to transfer fatty acids across the outer membrane.
In similar studies using rat liver contact sites, in addition to the mtOM proteins described above, mitochondrial inner membrane (mtIM) proteins, the very-long chain acyl-CoA dehydrogenase, the phosphate carrier, and the adenine nucleotide translocase 2 were present in association with CPT1a, ACSL, and VDAC. The 960 kDa to 600 kDa bands also contained the mtIM trifunctional protein, but the carnitine-acylcarnitine translocase was found only in lighter bands.
The control of palmitoylcarnitine oxidation in normal liver mitochondria was investigated. The main product of liver mitochondrial palmitoylcarnitine oxidation was either citrate or acetoacetate, depending of the availability of a source of oxaloacetate. The conversion of one equivalent of palmitate to carbon dioxide and water requires 46 equivalents of atomic oxygen. When citrate is the end product 22 units of atomic oxygen will be used per unit of palmitate. When only acetoacetate is being formed, oxygen consumption is linked only to the dehydrogenations in β-oxidation and 14 oxygen atoms will be used. In the presence of rotenone to inhibit NADH oxidation and in the presence of oxaloacetate, palmitate oxidation is limited to the acyl-CoA dehydrogenase step and only 7 equivalents of atomic oxygen are used. In rat liver mitochondria, the rate of utilization of palmitoylcarnitine (4.3-4.4 nmoles/min/mg) was not affected by the kind of product to which it was converted. In contrast, heart mitochondria oxidized palmitoylcarnitine past citrate, while skeletal muscle have complete oxidation using 46 equivalents of atomic oxygen.
Labels: MiParea: Respiration
Organism: Rat Tissue;cell: Liver
Coupling state: OXPHOS Pathway: F, N, S HRR: Oxygraph-2k
- Center Mitochondrial Diseases; Dep7 Pharmacology Medicine; Case Western Reserve Univ School Medicine, Cleveland, Ohio, USA. - email@example.com
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