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Investigation of mitochondrial biogenesis defects in single substantia nigra neurons using post-mortem human tissues

Lookup NU author(s): Dr Chun ChenORCiD, Dr Amy VincentORCiD, Dr Alasdair Blain, Anna Smith, Emeritus Professor Doug Turnbull, Dr Amy Reeve



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2019 The Authors. Mitochondrial respiratory chain deficiency and mitochondrial DNA deletions are reported in substantia nigra neurons from healthy aged and Parkinson's disease cases, with extensive neuronal loss only seen in the latter. This study aimed to understand the pathological relevance of mitochondrial defects for neuronal survival. Using post-mortem human midbrain, substantia nigra neurons exposed to different types of mitochondrial defects (including mitochondrial DNA point mutations, single and multiple deletions) were compared to neurons from healthy aged and Parkinson's disease cases (either sex) at a single neuronal level. We identified mitochondrial deficiencies in all cases, though these deficiencies were more severe in the mitochondrial disease patients with multiple deletions. A significant reduction in TFAM expression was detected in Parkinson's disease compared to cases with other mitochondrial defects. Higher mitochondrial DNA copy number was detected in healthy aged neurons, despite a deletion level equivalent to Parkinson's disease. Our data support that in individuals with pathogenic mitochondrial defects, neurons respond to mitochondrial defect to survive and such an adaptation may involve TFAM.

Publication metadata

Author(s): Chen C, Vincent AE, Blain AP, Smith AL, Turnbull DM, Reeve AK

Publication type: Article

Publication status: Published

Journal: Neurobiology of Disease

Year: 2020

Volume: 134

Print publication date: 01/02/2020

Online publication date: 02/11/2019

Acceptance date: 01/10/2019

Date deposited: 15/11/2019

ISSN (print): 0969-9961

ISSN (electronic): 1095-953X

Publisher: Academic Press Inc.


DOI: 10.1016/j.nbd.2019.104631


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Funder referenceFunder name
MR/L016354/1Medical Research Council (MRC)