What question did this study set out to answer?

To evaluate the impact of oxidative post-translational modifications on mitochondrial AAA+ protease LONP1 and investigate its role in pressure overload-induced heart failure.

April 17, 2014Circulation Heart FailureOpen Access

Oxidative Post-Translational Modifications Develop LONP1 Dysfunction in Pressure Overload Heart Failure

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Authors

AHAtsushi HoshinoKyoto Prefectural University of Medicine YOYoshifumi OkawaKyoto Medical Center MAMakoto AriyoshiKyoto Prefectural University of Medicine

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Implication

Animal study demonstrates that oxidative inactivation of mitochondrial LONP1 protease drives cardiac dysfunction in pressure overload mice, highlighting antioxidant targeting for heart failure.

Key Points

To evaluate the impact of oxidative post-translational modifications on mitochondrial AAA+ protease LONP1 and investigate its role in pressure overload-induced heart failure.
Assessed ATP-dependent mitochondrial proteolytic activity, LONP1 oxidative modifications (cysteine reduction, tyrosine nitration, and carbonylation), and electron transport chain turnover in a mouse model of pressure overload heart failure.
Evaluated mitochondrial energetics and left ventricular contractility after interventions with mitochondria-targeted human catalase, the superoxide dismutase mimetic mitoTEMPO, or LONP1 siRNA knockdown.
Failing heart mitochondria showed reduced ATP-dependent proteolysis alongside increased LONP1 tyrosine nitration and carbonylation, causing accumulation of oxidatively damaged electron transport chain proteins despite decreased mRNA levels.
Treatment with mitochondria-targeted human catalase or mitoTEMPO reversed LONP1 oxidative modifications, restored electron transport chain homeostasis, and improved mitochondrial respiration and cardiac contractility.
In vivo siRNA repression of LONP1 partially abrogated the cardioprotective and mitochondrial benefits provided by mitochondria-targeted catalase and mitoTEMPO.

Cite This Study

Hoshino et al. (2014) studied this question.

synapsesocial.com/papers/6aa9236f6db186eb9162e07e https://doi.org/10.1161/circheartfailure.113.001062

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Implication

Animal study demonstrates that oxidative inactivation of mitochondrial LONP1 protease drives cardiac dysfunction in pressure overload mice, highlighting antioxidant targeting for heart failure.

Oxidative Post-Translational Modifications Develop LONP1 Dysfunction in Pressure Overload Heart Failure

Discussion

Member takes

Implication

Key Points

Cite This Study

Oxidative Post-Translational Modifications Develop LONP1 Dysfunction in Pressure Overload Heart Failure

Discussion

Member takes

Implication

Key Points

Cite This Study

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