DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion
Por:
Gallinat, A, Rakovic, A, Klein, C, Badimon, L
Publicada:
20 nov 2022
Ahead of Print:
1 nov 2022
Resumen:
The early-onset Parkinson's disease protein DJ-1 is a multifunctional protein that plays a protective role against ischemia and reperfusion (I/R) injury and oxidative stress. Despite lacking a canonical RNA-binding domain DJ-1 exhibits RNA-binding activity and multiple transcripts have been identified. However, no functional charac-terization has been provided to date. Here, we have investigated the DJ-1-interacting transcripts, as well as the role of DJ-1 RNA-binding activity during ischemia and reperfusion. Among the identified DJ-1-interacting transcripts, we have distinguished a significant enrichment of mRNAs encoding mitochondrial proteins. The effects of DJ-1 depletion on mitochondrial protein expression and mitochondrial morphology were investigated using a CRISPR/Cas9 generated DJ-1 knockout (DJ-1KO) cell model. DJ-1 depletion resulted in increased MTND2 protein expression in resting cells; however, after exposure to I/R, MTND2 levels were significantly reduced with respect to wild type cells. Increased mitochondrial fission was consistently found in DJ-1KO cells after I/R exposure. MTND2 transcript binding to DJ-1 was increased during ischemia. Our results indicate that the RNA -binding activity of DJ-1 shield mitochondrial transcripts from oxidative damage.
Filiaciones:
Gallinat, A:
IR Hosp Santa Creu i St Pau, Cardiovasc Program ICCC, IIB Sant Pau, Barcelona, Spain
Univ Autonoma Barcelona UAB, Barcelona, Spain
Rakovic, A:
Univ Lubeck, Inst Neurogenet, Lubeck, Germany
Klein, C:
Univ Lubeck, Inst Neurogenet, Lubeck, Germany
Badimon, L:
IR Hosp Santa Creu i St Pau, Cardiovasc Program ICCC, IIB Sant Pau, Barcelona, Spain
Inst Salud Carlos III, CIBERCV, Madrid, Spain
UAB Chair Cardiovasc Res, Barcelona, Spain
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