ORP5 promotes cardiac hypertrophy by regulating the activation of mTORC1 on lysosome
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View abstract on PubMed
Summary
This summary is machine-generated.Oxysterol binding protein (OSBP)-related protein 5 (ORP5) drives pathological cardiac hypertrophy by moving mTORC1 to lysosomes. Reducing ORP5 improves heart function, offering a potential therapeutic target.
Area Of Science
- Cardiovascular Biology
- Molecular Cardiology
- Cell Signaling
Background
- Oxysterol binding protein (OSBP)-related protein 5 (ORP5) is a lipid transfer protein at membrane contact sites.
- ORP5 activates mTORC1 signaling, promoting cell proliferation.
- The role of ORP5 in pathological cardiac hypertrophy is not well understood.
Purpose Of The Study
- To investigate the role of ORP5 in pathological cardiac hypertrophy.
- To elucidate the regulatory mechanisms of ORP5 on mTORC1 in hypertrophied hearts.
Main Methods
- Utilized AAV9-treated mice and neonatal rat ventricular myocytes (NRVMs).
- Assessed cardiac function, morphology, and mTORC1 signaling.
- Employed molecular techniques to determine ORP5's regulatory mechanisms on mTORC1.
Main Results
- ORP5 expression increased in hypertrophic cardiomyopathy (HCM) hearts, TAC mice, and AngII-treated NRVMs.
- ORP5 deficiency improved cardiac function and reduced hypertrophy; ORP5 overexpression aggravated it.
- ORP5 facilitates pathological hypertrophy by translocating mTORC1 to the lysosome for activation.
Conclusions
- ORP5 promotes pathological ventricular hypertrophy via lysosomal mTORC1 translocation and activation.
- ORP5 presents potential as a diagnostic biomarker or therapeutic target for cardiac hypertrophy.
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