Cardiolipin deficiency releases cytochrome c from the inner mitochondrial membrane and accelerates stimuli-elicited apoptosis

The gastrocnemius, a fast-twitch white muscle, and the soleus, a slow-twitch red muscle, were studied in A/J mice. The specific activities of the lysosomal hydrolases, beta-D-glucuronidase, hexosaminidase, beta-D-galactosidase and arylsulphatase, the inner-mitochondrial-membrane enzyme cytochrome c oxidase, and the outer-mitochondrial-membrane enzyme monoamine oxidase, were greater in the soleus than in the gastrocnemius. The specific activities of the lysosomal hydrolases and cytochrome c oxidase in the gastrocnemius and soleus were substantially higher in male mice than in female mice. Orchiectomy abolished this sex difference. Testosterone increased the activities of the lysosomal hydrolases and cytochrome c oxidase and coincidentally induced muscle hypertrophy and an accretion of protein and RNA, but total DNA remained constant. Monoamine oxidase was unaffected by sex, orchiectomy and testosterone. These findings indicate that endogenous androgens regulate the activity of enzymes associated with lysosomes and the inner mitochondrial membrane, as well as muscle fibre growth in mouse skeletal muscle.

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Complex formation by cytochrome c : A clue to the structure and polarity of the inner mitochondrial membrane

FEBS Letters ◽

10.1016/0014-5793(69)80147-x ◽

1969 ◽

Vol 3 (4) ◽

pp. 242-246 ◽

Cited By ~ 35

Author(s):

P. Nicholls ◽

E. Mochan ◽

H.K. Kimelberg

Keyword(s):

Cytochrome C ◽

Complex Formation ◽

Mitochondrial Membrane ◽

Inner Mitochondrial Membrane

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Role of cytochrome c heme lyase in mitochondrial import and accumulation of cytochrome c in Saccharomyces cerevisiae.

Molecular and Cellular Biology ◽

10.1128/mcb.11.11.5487 ◽

1991 ◽

Vol 11 (11) ◽

pp. 5487-5496 ◽

Cited By ~ 105

Author(s):

M E Dumont ◽

T S Cardillo ◽

M K Hayes ◽

F Sherman

Keyword(s):

Saccharomyces Cerevisiae ◽

Cytochrome C ◽

Mitochondrial Membrane ◽

Intermembrane Space ◽

Inner Mitochondrial Membrane ◽

Yeast Saccharomyces Cerevisiae ◽

Apocytochrome C ◽

Cytochrome C Heme Lyase

Heme is covalently attached to cytochrome c by the enzyme cytochrome c heme lyase. To test whether heme attachment is required for import of cytochrome c into mitochondria in vivo, antibodies to cytochrome c have been used to assay the distributions of apo- and holocytochromes c in the cytoplasm and mitochondria from various strains of the yeast Saccharomyces cerevisiae. Strains lacking heme lyase accumulate apocytochrome c in the cytoplasm. Similar cytoplasmic accumulation is observed for an altered apocytochrome c in which serine residues were substituted for the two cysteine residues that normally serve as sites of heme attachment, even in the presence of normal levels of heme lyase. However, detectable amounts of this altered apocytochrome c are also found inside mitochondria. The level of internalized altered apocytochrome c is decreased in a strain that completely lacks heme lyase and is greatly increased in a strain that overexpresses heme lyase. Antibodies recognizing heme lyase were used to demonstrate that the enzyme is found on the outer surface of the inner mitochondrial membrane and is not enriched at sites of contact between the inner and outer mitochondrial membranes. These results suggest that apocytochrome c is transported across the outer mitochondrial membrane by a freely reversible process, binds to heme lyase in the intermembrane space, and is then trapped inside mitochondria by an irreversible conversion to holocytochrome c accompanied by folding to the native conformation. Altered apocytochrome c lacking the ability to have heme covalently attached accumulates in mitochondria only to the extent that it remains bound to heme lyase.

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Mitochondrial cytochrome c oxidase: catalysis, coupling and controversies

Biochemical Society Transactions ◽

10.1042/bst20160139 ◽

2017 ◽

Vol 45 (3) ◽

pp. 813-829 ◽

Cited By ~ 38

Author(s):

Peter R. Rich

Keyword(s):

Cytochrome C ◽

Cytochrome C Oxidase ◽

Mitochondrial Membrane ◽

Mitochondrial Cytochrome ◽

Inner Mitochondrial Membrane ◽

Reaction Cycle ◽

Chemical Structures ◽

Catalytic Intermediates ◽

Underlying Mechanisms ◽

Mitochondrial Cytochrome C

Mitochondrial cytochrome c oxidase is a member of a diverse superfamily of haem–copper oxidases. Its mechanism of oxygen reduction is reviewed in terms of the cycle of catalytic intermediates and their likely chemical structures. This reaction cycle is coupled to the translocation of protons across the inner mitochondrial membrane in which it is located. The likely mechanism by which this occurs, derived in significant part from studies of bacterial homologues, is presented. These mechanisms of catalysis and coupling, together with current alternative proposals of underlying mechanisms, are critically reviewed.

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Idebenone-Induced Recovery of Glycerol-3-Phosphate and Succinate Oxidation Inhibited by Digitonin

Physiological Research ◽

10.33549/physiolres.932318 ◽

2012 ◽

pp. 259-265 ◽

Cited By ~ 5

Author(s):

H. RAUCHOVÁ ◽

M. VOKURKOVÁ ◽

Z. DRAHOTA

Keyword(s):

Oxygen Consumption ◽

Cytochrome C ◽

Oxidation Rate ◽

Mitochondrial Membrane ◽

Synthetic Analog ◽

Active Components ◽

Inner Mitochondrial Membrane ◽

Succinate Oxidation ◽

Consumption Rates ◽

Cyt C

Digitonin solubilizes mitochondrial membrane, breaks the integrity of the respiratory chain and releases two mobile redox-active components: coenzyme Q (CoQ) and cytochrome c (cyt c). In the present study we report the inhibition of glycerol-3-phosphate- and succinate-dependent oxygen consumption rates by digitonin treatment. Our results show that the inhibition of oxygen consumption rates is recovered by the addition of exogenous synthetic analog of CoQ idebenone (hydroxydecyl-ubiquinone; IDB) and cyt c. Glycerol-3-phosphate oxidation rate is recovered to 148 % of control values, whereas succinate-dependent oxidation rate only to 68 %. We find a similar effect on the activities of glycerol-3-phosphate and succinate cytochrome c oxidoreductase. Our results also indicate that succinate-dependent oxidation is less sensitive to digitonin treatment and less activated by IDB in comparison with glycerol-3-phosphate-dependent oxidation. These findings might indicate the different mechanism of the electron transfer from two flavoprotein-dependent dehydrogenases (glycerol-3-phosphate dehydrogenase and succinate dehydrogenase) localized on the outer and inner face of the inner mitochondrial membrane, respectively.

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Resolution and Reconstitution of a Mammalian Membrane

The Journal of General Physiology ◽

10.1085/jgp.54.1.38 ◽

1969 ◽

Vol 54 (1) ◽

pp. 38-49 ◽

Cited By ~ 15

Author(s):

Efraim Racker

Keyword(s):

Cytochrome C ◽

Oxidative Phosphorylation ◽

Succinate Dehydrogenase ◽

Mitochondrial Membrane ◽

Inner Mitochondrial Membrane ◽

Submitochondrial Particles ◽

Highly Sensitive ◽

Cytochrome C1 ◽

Coupling Factors ◽

Oxidation Chain

The problem of the resolution and reconstitution of the inner mitochondrial membrane has been approached at three levels. (1) Starting with phosphorylating submitochondrial particles, a "resolution from without" can be achieved by stripping of surface components. The most extensive resolution was recently obtained with the aid of silicotungstate. Such particles require for oxidative phosphorylation the addition of several coupling factors as well as succinate dehydrogenase. (2) Starting with submitochondrial particles that have been degraded by trypsin and urea a resolution of the inner membrane proper containing an ATPase has been achieved. These experiments show that at least five components are required for the reconstitution of an oligomycin-sensitive ATPase: a particulate component, F1, Mg++, phospholipids, and Fc. Morphologically, the reconstituted ATPase preparations resemble submitochondrial particles. (3) Starting with intact mitochondria individual components of the oxidation chain have been separated from each other. The following components were required for the reconstitution of succinoxidase: succinate dehydrogenase, cytochrome b\, cytochrome c1, cytochrome c, cytochrome oxidase, phospholipids and Q10. The reconstituted complex had properties similar to those of phosphorylating submitochondrial particles; i.e., the oxidation of succinate by molecular oxygen was highly sensitive to antimycin.

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