Mitochondrial dysfunction in adult midbrain dopamine neurons triggers an early immune response
Artikel i vetenskaplig tidskrift, 2021

Dopamine (DA) neurons of the midbrain are at risk to become affected by mitochondrial damage over time and mitochondrial defects have been frequently reported in Parkinson's disease (PD) patients. However, the causal contribution of adult-onset mitochondrial dysfunction to PD remains uncertain. Here, we developed a mouse model lacking Mitofusin 2 (MFN2), a key regulator of mitochondrial network homeostasis, in adult midbrain DA neurons. The knockout mice develop severe and progressive DA neuron-specific mitochondrial dysfunction resulting in neurodegeneration and parkinsonism. To gain further insights into pathophysiological events, we performed transcriptomic analyses of isolated DA neurons and found that mitochondrial dysfunction triggers an early onset immune response, which precedes mitochondrial swelling, mtDNA depletion, respiratory chain deficiency and cell death. Our experiments show that the immune response is an early pathological event when mitochondrial dysfunction is induced in adult midbrain DA neurons and that neuronal death may be promoted non-cell autonomously by the cross-talk and activation of surrounding glial cells.

Författare

Roberta Filograna

Karolinska Institutet

Seungmin Lee

Karolinska Institutet

Katarína Tiklová

Karolinska Institutet

Mara Mennuni

Karolinska Institutet

Viktor Jonsson

Chalmers, Biologi och bioteknik, Systembiologi, CSBI

Markus Ringnér

Lunds universitet

Linda Gillberg

Karolinska Institutet

Elena Sopova

Saint Petersburg State University - Spsu

Karolinska Institutet

Oleg Shupliakov

Karolinska Institutet

Saint Petersburg State University - Spsu

Camilla Koolmeister

Karolinska Institutet

L Olson

Karolinska Institutet

Thomas Perlmann

Karolinska Institutet

Nils-Göran Larsson

Karolinska Institutet

PLoS Genetics

1553-7390 (ISSN) 1553-7404 (eISSN)

Vol. 17 9 e1009822

Ämneskategorier

Neurovetenskaper

Cell- och molekylärbiologi

Immunologi inom det medicinska området

DOI

10.1371/journal.pgen.1009822

PubMed

34570766

Mer information

Senast uppdaterat

2021-11-11