Journal Article

DKFZ-2021-00043

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Autophagy inhibition rescues structural and functional defects caused by the loss of mitochondrial chaperone Hsc70-5 in Drosophila.

Zhu, J.-Y. ; Hannan, S. B.DKFZ* ; Dräger, N.DKFZ* ; Vereshchagina, N. ; Krahl, A.-C. ; Fu, Y. ; Elliott, C. J. H. ; Han, Z. ; Jahn, T.DKFZ* ; Rasse, T. (Last author)DKFZ*

2021
Taylor & Francis Abingdon, Oxon

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Please use a persistent id in citations: doi:10.1080/15548627.2020.1871211

Abstract: We investigated in larval and adult Drosophila models whether loss of the mitochondrial chaperone Hsc70-5 is sufficient to cause pathological alterations commonly observed in Parkinson disease. At affected larval neuromuscular junctions, no effects on terminal size, bouton size or number, synapse size, or number were observed, suggesting that we studied an early stage of pathogenesis. At this stage, we noted a loss of synaptic vesicle proteins and active zone components, delayed synapse maturation, reduced evoked and spontaneous excitatory junctional potentials, increased synaptic fatigue, and cytoskeleton rearrangements. The adult model displayed ATP depletion, altered body posture, and susceptibility to heat-induced paralysis. Adult phenotypes could be suppressed by knockdown of dj-1β, Lrrk, DCTN2-p50, DCTN1-p150, Atg1, Atg101, Atg5, Atg7, and Atg12. The knockdown of components of the macroautophagy/autophagy machinery or overexpression of human HSPA9 broadly rescued larval and adult phenotypes, while disease-associated HSPA9 variants did not. Overexpression of Pink1 or promotion of autophagy exacerbated defects.

Keyword(s): Atg1 ; Hsc70-5 ; microtubule ; mitochondria ; mitophagy ; rapamycin ; synapse

Note: #LA:B180# /2021 Oct;17(10):3160-3174

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Contributing Institute(s):

1. Proteostase neurodegenerativer Erkrankungen (B180)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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