COMP-prohibitin 2 interaction maintains mitochondrial homeostasis and controls smooth muscle cell identity.
Cell Death Dis
; 9(6): 676, 2018 06 04.
Article
em En
| MEDLINE
| ID: mdl-29867124
ABSTRACT
Vascular smooth muscle cells (VSMCs) are highly phenotypically plastic, and loss of the contractile phenotype in VSMCs has been recognized at the early onset of the pathology of a variety of vascular diseases. However, the endogenous regulatory mechanism to maintain contractile phenotype in VSMCs remains elusive. Moreover, little has been known about the role of the mitochondrial bioenergetics in terms of VSMC homeostasis. Herein, we asked if glycoprotein COMP (Cartilage oligomeric matrix protein) is involved in mitochondrial bioenergetics and therefore regulates VSMCs homeostasis. By using fluorescence assay, subcellular western blot and liquid chromatography tandem mass spectrometry analysis, we found that extracellular matrix protein COMP unexpectedly localized within mitochondria. Further mitochondrial transplantation revealed that both mitochondrial and non-mitochondrial COMP maintained VSMC identity. Moreover, microarray analysis revealed that COMP deficiency impaired mitochondrial oxidative phosphorylation in VSMCs. Further study confirmed that COMP deficiency caused mitochondrial oxidative phosphorylation dysfunction accompanied by morphological abnormality. Moreover, the interactome of mitochondrial COMP revealed that COMP interacted with prohibitin 2, and COMP-prohibitin 2 interaction maintained mitochondrial homeostasis. Additionally, disruption of COMP-prohibitin 2 interaction caused VSMC dedifferentiation in vitro and enhanced the neointima formation post rat carotid artery injury in vivo. In conclusion, COMP-prohibitin 2 interaction in mitochondria plays an important role in maintaining the contractile phenotype of VSMCs by regulating mitochondrial oxidative phosphorylation. Maintaining the homeostasis of mitochondrial respiration through COMP-prohibitin 2 interaction may shed light on prevention of vascular disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Miócitos de Músculo Liso
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Proteína de Matriz Oligomérica de Cartilagem
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Homeostase
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Mitocôndrias
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article