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Mitochondrial Phenotypes in Parkinson’s Diseases—A Focus on Human iPSC-Derived Dopaminergic Neurons

Biomedical Center (BMC), Division of Metabolic Biochemistry, Faculty of Medicine, Ludwig-Maximilians-Universität München, 81337 Munich, Germany
Max Planck Institute of Neurobiology, 82152 Martinsried, Germany
Institute of Neuronal Cell Biology, Technical University of Munich, 80333 Munich, Germany
Munich Cluster for Systems Neurology (SyNergy), 81337 Munich, Germany
German Center for Neurodegenerative Diseases (DZNE), 81337 Munich, Germany
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Alfonso Eirin
Cells 2021, 10(12), 3436;
Received: 2 November 2021 / Revised: 29 November 2021 / Accepted: 2 December 2021 / Published: 7 December 2021
(This article belongs to the Special Issue Mitochondrial Functions in Stem Cells)
Established disease models have helped unravel the mechanistic underpinnings of pathological phenotypes in Parkinson’s disease (PD), the second most common neurodegenerative disorder. However, these discoveries have been limited to relatively simple cellular systems and animal models, which typically manifest with incomplete or imperfect recapitulation of disease phenotypes. The advent of induced pluripotent stem cells (iPSCs) has provided a powerful scientific tool for investigating the underlying molecular mechanisms of both familial and sporadic PD within disease-relevant cell types and patient-specific genetic backgrounds. Overwhelming evidence supports mitochondrial dysfunction as a central feature in PD pathophysiology, and iPSC-based neuronal models have expanded our understanding of mitochondrial dynamics in the development and progression of this devastating disorder. The present review provides a comprehensive assessment of mitochondrial phenotypes reported in iPSC-derived neurons generated from PD patients’ somatic cells, with an emphasis on the role of mitochondrial respiration, morphology, and trafficking, as well as mitophagy and calcium handling in health and disease. Furthermore, we summarize the distinguishing characteristics of vulnerable midbrain dopaminergic neurons in PD and report the unique advantages and challenges of iPSC disease modeling at present, and for future mechanistic and therapeutic applications. View Full-Text
Keywords: Parkinson’s disease; iPSC; mitochondria; dopaminergic neurons Parkinson’s disease; iPSC; mitochondria; dopaminergic neurons
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MDPI and ACS Style

Heger, L.M.; Wise, R.M.; Hees, J.T.; Harbauer, A.B.; Burbulla, L.F. Mitochondrial Phenotypes in Parkinson’s Diseases—A Focus on Human iPSC-Derived Dopaminergic Neurons. Cells 2021, 10, 3436.

AMA Style

Heger LM, Wise RM, Hees JT, Harbauer AB, Burbulla LF. Mitochondrial Phenotypes in Parkinson’s Diseases—A Focus on Human iPSC-Derived Dopaminergic Neurons. Cells. 2021; 10(12):3436.

Chicago/Turabian Style

Heger, Leonie M., Rachel M. Wise, J. Tabitha Hees, Angelika B. Harbauer, and Lena F. Burbulla. 2021. "Mitochondrial Phenotypes in Parkinson’s Diseases—A Focus on Human iPSC-Derived Dopaminergic Neurons" Cells 10, no. 12: 3436.

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