The Cytomegalovirus protein pUL37×1 targets mitochondria to mediate neuroprotection

Chien Tai Hong, Kai Yin Chau, Anthony H V Schapira

Research output: Contribution to journalArticle

Abstract

There is substantial evidence that mitochondrial dysfunction plays a significant role in the pathogenesis of Parkinson disease (PD). This contribution probably encompasses defects of oxidative phosphorylation, mitochondrial turnover (mitophagy), mitochondrial derived oxidative stress, and apoptotic signalling. Human cytomegalovirus immediate-early protein pUL37 × 1 induces Bax mitochondrial translocation and inactivation to prevent apoptosis. Over-expressing pUL37 × 1 in neuronal cells protects against staurosporin and 6-hydroxydopamine induced apoptosis and cell death. Protection is not enhanced by bax silencing in pUL37 × 1 over-expressing cells, suggesting a bax-dependent mechanism of action. pUL37 × 1 increases glycolysis and induces mitochondrial hyperpolarization, a bax independent anti-apoptotic action. pUL37 × 1 increases glycolysis through activation of phosphofructokinase by a calcium-dependent pathway. The dual anti-apoptotic mechanism of pUL37 × 1 may be considered a novel neuroprotective strategy in diseases where mitochondrial dysfunction and apoptotic pathways are involved.

Original languageEnglish
Article number31373
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Aug 26 2016

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Glycolysis
Cytomegalovirus
Mitochondria
Mitochondrial Degradation
Apoptosis
Mitochondrial Turnover
Phosphofructokinases
Mitochondrial Diseases
Oxidopamine
Oxidative Phosphorylation
Parkinson Disease
Proteins
Oxidative Stress
Cell Death
Calcium
Neuroprotection
cytomegalovirus IE1 protein

ASJC Scopus subject areas

  • General

Cite this

The Cytomegalovirus protein pUL37×1 targets mitochondria to mediate neuroprotection. / Hong, Chien Tai; Chau, Kai Yin; Schapira, Anthony H V.

In: Scientific Reports, Vol. 6, 31373, 26.08.2016.

Research output: Contribution to journalArticle

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