Mutations in PTEN inducible kinase-1 (PINK1) induce mitochondrial dysfunction in dopaminergic neurons resulting in an inherited form of Parkinson's disease. Although PINK1 is present in the heart its exact role there is unclear. We hypothesized that PINK1 protects the heart against acute ischemia reperfusion injury (IRI) by preventing mitochondrial dysfunction

Angelova, PR

Burke, N

Davidson, SM

Deas, E

Hall, AR

Hausenloy, DJ

Ludtmann, MH

Mocanu, MM

Mukherjee, UA

Ong, SB

Siddall, HK

Yellon, DM

PLoS ONE

PubMed

Objectives:Mutations in PTEN inducible kinase-1 (PINK1) induce mitochondrial dysfunction in dopaminergic neurons resulting in an inherited form of Parkinson's disease. Although PINK1 is present in the heart its exact role there is unclear. We hypothesized that PINK1 protects the heart against acute ischemia reperfusion injury (IRI) by preventing mitochondrial dysfunction.Methods and Results:Over-expressing PINK1 in HL-1 cardiac cells reduced cell death following simulated IRI (29.2±5.2% PINK1 versus 49.0±2.4% control; N = 320 cells/group P5 animals/group; P<0.05). Cardiomyocytes isolated from PINK1-/- hearts had a lower resting mitochondrial membrane potential, had inhibited mitochondrial respiration, generated more oxidative stress during simulated IRI, and underwent rigor contracture more rapidly in response to an uncoupler when compared to PINK1+/+ cells suggesting mitochondrial dysfunction in hearts deficient in PINK1.Conclusions:We show that the loss of PINK1 increases the heart's vulnerability to ischemia-reperfusion injury. This may be due, in part, to increased mitochondrial dysfunction. These findings implicate PINK1 as a novel target for cardioprotectio

Siddall, Hilary K.

Yellon, Derek M.

Ong, Sang Bing

Mukherjee, Uma A.

Burke, Niall

Hall, Andrew R.

Angelova, Plamena R.

Ludtmann, Marthe H. R.

Deas, Emma

Davidson, Sean M.

Mocanu, Mihaela M.

Hausenloy, Derek J.

Universiti Teknologi Malaysia Institutional Repository

Loss of PINK1 increases the heart's vulnerability to ischemia-reperfusion injury

UCL Discovery

Loss of PINK1 Increases the Heart's Vulnerability to Ischemia-Reperfusion Injury.

Mutations in PTEN inducible kinase-1 (PINK1) induce mitochondrial dysfunction in dopaminergic neurons resulting in an inherited form of Parkinson's disease. Although PINK1 is present in the heart its exact role there is unclear. We hypothesized that PINK1 protects the heart against acute ischemia reperfusion injury (IRI) by preventing mitochondrial dysfunction.Over-expressing PINK1 in HL-1 cardiac cells reduced cell death following simulated IRI (29.2±5.2% PINK1 versus 49.0±2.4% control; N = 320 cells/group P5 animals/group; P<0.05). Cardiomyocytes isolated from PINK1-/- hearts had a lower resting mitochondrial membrane potential, had inhibited mitochondrial respiration, generated more oxidative stress during simulated IRI, and underwent rigor contracture more rapidly in response to an uncoupler when compared to PINK1+/+ cells suggesting mitochondrial dysfunction in hearts deficient in PINK1.We show that the loss of PINK1 increases the heart's vulnerability to ischemia-reperfusion injury. This may be due, in part, to increased mitochondrial dysfunction. These findings implicate PINK1 as a novel target for cardioprotection

Hilary K Siddall

Derek M Yellon

Sang-Bing Ong

Uma A Mukherjee

Niall Burke

Andrew R Hall

Plamena R Angelova

Marthe H R Ludtmann

Emma Deas

Sean M Davidson

Mihaela M Mocanu

Derek J Hausenloy

Directory of Open Access Journals

Loss of PINK1 increases the heart's vulnerability to ischemia-reperfusion injury.

http://eprints.utm.my/id/eprint/49047/1/OngSangBing2013_LossofPINK1increases.pdf

Loss of PINK1 Increases the Heart's Vulnerability to Ischemia-Reperfusion Injury.

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Universiti Teknologi Malaysia Institutional Repository

UCL Discovery

Directory of Open Access Journals