Miro1 Marks Parkinson's Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson's Models

Chung Han Hsieh, Li Li, Roeland Vanhauwaert, Kong T. Nguyen, Mary D. Davis, Guojun Bu, Zbigniew K. Wszolek, Xinnan Wang

Research output: Contribution to journalArticle

Abstract

The identification of molecular targets and pharmacodynamic markers for Parkinson's disease (PD) will empower more effective clinical management and experimental therapies. Miro1 is localized on the mitochondrial surface and mediates mitochondrial motility. Miro1 is removed from depolarized mitochondria to facilitate their clearance via mitophagy. Here, we explore the clinical utility of Miro1 for detecting PD and for gauging potential treatments. We measure the Miro1 response to mitochondrial depolarization using biochemical assays in skin fibroblasts from a broad spectrum of PD patients and discover that more than 94% of the patients’ fibroblast cell lines fail to remove Miro1 following depolarization. We identify a small molecule that can repair this defect of Miro1 in PD fibroblasts. Treating patient-derived neurons and fly models with this compound rescues the locomotor deficits and dopaminergic neurodegeneration. Our results indicate that tracking this Miro1 marker and engaging in Miro1-based therapies could open new avenues to personalized medicine.

Original languageEnglish (US)
Pages (from-to)1131-1140.e7
JournalCell Metabolism
Volume30
Issue number6
DOIs
StatePublished - Dec 3 2019

Fingerprint

Parkinson Disease
Neurons
Fibroblasts
Mitochondrial Degradation
Precision Medicine
Investigational Therapies
Diptera
Mitochondria
Cell Line
Skin
Therapeutics

Keywords

  • biomarker
  • diet
  • fibroblast
  • fly
  • iPSC
  • Miro1
  • mitochondria
  • mitophagy
  • neurons
  • Parkinson
  • small molecules
  • therapy

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Hsieh, C. H., Li, L., Vanhauwaert, R., Nguyen, K. T., Davis, M. D., Bu, G., ... Wang, X. (2019). Miro1 Marks Parkinson's Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson's Models. Cell Metabolism, 30(6), 1131-1140.e7. https://doi.org/10.1016/j.cmet.2019.08.023

Miro1 Marks Parkinson's Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson's Models. / Hsieh, Chung Han; Li, Li; Vanhauwaert, Roeland; Nguyen, Kong T.; Davis, Mary D.; Bu, Guojun; Wszolek, Zbigniew K.; Wang, Xinnan.

In: Cell Metabolism, Vol. 30, No. 6, 03.12.2019, p. 1131-1140.e7.

Research output: Contribution to journalArticle

Hsieh, Chung Han ; Li, Li ; Vanhauwaert, Roeland ; Nguyen, Kong T. ; Davis, Mary D. ; Bu, Guojun ; Wszolek, Zbigniew K. ; Wang, Xinnan. / Miro1 Marks Parkinson's Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson's Models. In: Cell Metabolism. 2019 ; Vol. 30, No. 6. pp. 1131-1140.e7.
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