Mitochondrial calcium dysfunction contributes to autophagic cell death induced by MPP+ via AMPK pathway.

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Prevailing evidence suggests that abnormal autophagy and mitochondrial dysfunction participate in the process of PD. However, many damages of neuronal functions are regulated by intracellular Ca2+ signaling and the contribution of mitochondrial Ca2+ to the process of neurodegeneration is still unclear. MPP+, the metabolite of a neurotoxin MPTP, causes symptom of PD in animal models by selectively destroying dopaminergic neurons in substantia nigra. Here we report that mitochondrial Ca2+ uniporter (MCU) participated in MPP+-induced autophagic cell death in SH-SY5Y cells. Pharmacological agonist of MCU or exogenous expressed MCU can partially reduce MPP+-induced autophagic cell death. Down-regulation of MCU enhanced autophagic cell death via AMPK activation, which was independent of Beclin1 and PI3K. These findings show that the mitochondrial calcium dyshomeostasis contributes to MPP+-induced neuronal degeneration, and MCU may be a potential therapeutic target of PD through the prevention of pathological autophagy.

• Publication year

  2019

• Venue

  Biochemical and Biophysical Research Communications - BBRC

• Publication date

  2019-02-05

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.bbrc.2018.12.148PMID 30594390
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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