Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Ignatenko 2018 Nat Commun

From Bioblast
Publications in the MiPMap
Ignatenko O, Chilov D, Paetau I, de Miguel E, Jackson CB, Capin G, Paetau A, Terzioglu M, Euro L, Suomalainen A (2018) Loss of mtDNA activates astrocytes and leads to spongiotic encephalopathy. Nat Commun 9:70.

ยป PMID: 29302033 Open Access ยปO2k-brief

Ignatenko O, Chilov D, Paetau I, de Miguel E, Jackson CB, Capin G, Paetau A, Terzioglu M, Euro L, Suomalainen Anu (2018) Nat Commun

Abstract: Mitochondrial dysfunction manifests as different neurological diseases, but the mechanisms underlying the clinical variability remain poorly understood. To clarify whether different brain cells have differential sensitivity to mitochondrial dysfunction, we induced mitochondrial DNA (mtDNA) depletion in either neurons or astrocytes of mice, by inactivating Twinkle (TwKO), the replicative mtDNA helicase. Here we show that astrocytes, the most abundant cerebral cell type, are chronically activated upon mtDNA loss, leading to early-onset spongiotic degeneration of brain parenchyma, microgliosis and secondary neurodegeneration. Neuronal mtDNA loss does not, however, cause symptoms until 8 months of age. Findings in astrocyte-TwKO mimic neuropathology of Alpers syndrome, infantile-onset mitochondrial spongiotic encephalopathy caused by mtDNA maintenance defects. Our evidence indicates that (1) astrocytes are dependent on mtDNA integrity; (2) mitochondrial metabolism contributes to their activation; (3) chronic astrocyte activation has devastating consequences, underlying spongiotic encephalopathy; and that (4) astrocytes are a potential target for interventions.

โ€ข Bioblast editor: Kandolf G โ€ข O2k-Network Lab: FI Helsinki Suomalainen A


Labels: MiParea: Respiration, mtDNA;mt-genetics, Genetic knockout;overexpression  Pathology: Neurodegenerative  Stress:Mitochondrial disease  Organism: Mouse  Tissue;cell: Nervous system  Preparation: Homogenate 


Coupling state: OXPHOS, ET  Pathway: N, CIV, NS  HRR: Oxygraph-2k 

2018-01, O2k-brief, MitoFit 2021 Photosynthesis 

O2k-brief.png

O2k-brief

ยป List of O2k-Publications presented as O2k-brief

Cite by

  • Huete-Ortega et al (2021) Substrate-uncoupler-inhibitor-titration protocols for photosynthesis in Chlamydomonas reinhardtii. MitoFit Preprints 2021 (in prep).