Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction

Sophia Von Stockum, Alvaro Sanchez-Martinez, Samantha Corrà, Joy Chakraborty, Elena Marchesan, Lisa Locatello, Caterina Da Rè, Paola Cusumano, Federico Caicci, Vanni Ferrari, Rodolfo Costa, Luigi Bubacco, Maria Berica Rasotto, Ildiko Szabo, Alexander J. Whitworth, Luca Scorrano, Elena Ziviani

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aberrant mitochondrial dynamics disrupts mitochondrial function and contributes to disease conditions. A targeted RNA interference screen for deubiquitinating enzymes (DUBs) affecting protein levels of multifunctional mitochondrial fusion protein Mitofusin (MFN) identified USP8 prominently influencing MFN levels. Genetic and pharmacological inhibition of USP8 normalized the elevated MFN protein levels observed in PINK1 and Parkin-deficient models. This correlated with improved mitochondrial function, locomotor performance and life span, and prevented dopaminergic neurons loss in Drosophila PINK1 KO flies. We identified a novel target antagonizing pathologically elevated MFN levels, mitochondrial dysfunction, and dopaminergic neuron loss of a Drosophila model of mitochondrial dysfunction.

Original languageEnglish
Article numbere201900392
JournalLife Science Alliance
Volume2
Issue number2
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Mitochondrial Dynamics
Mitochondria
Dopaminergic Neurons
mitochondrion
Drosophila
mitochondria
Neurons
protein
Mitochondrial Proteins
RNA Interference
neurons
Diptera
Proteins
proteins
Pharmacology
RNA interference
RNA
Fusion reactions
enzyme
Enzymes

ASJC Scopus subject areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

Cite this

Von Stockum, S., Sanchez-Martinez, A., Corrà, S., Chakraborty, J., Marchesan, E., Locatello, L., ... Ziviani, E. (2019). Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction. Life Science Alliance, 2(2), [e201900392]. https://doi.org/10.26508/lsa.201900392

Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction. / Von Stockum, Sophia; Sanchez-Martinez, Alvaro; Corrà, Samantha; Chakraborty, Joy; Marchesan, Elena; Locatello, Lisa; Rè, Caterina Da; Cusumano, Paola; Caicci, Federico; Ferrari, Vanni; Costa, Rodolfo; Bubacco, Luigi; Rasotto, Maria Berica; Szabo, Ildiko; Whitworth, Alexander J.; Scorrano, Luca; Ziviani, Elena.

In: Life Science Alliance, Vol. 2, No. 2, e201900392, 01.01.2019.

Research output: Contribution to journalArticle

Von Stockum, S, Sanchez-Martinez, A, Corrà, S, Chakraborty, J, Marchesan, E, Locatello, L, Rè, CD, Cusumano, P, Caicci, F, Ferrari, V, Costa, R, Bubacco, L, Rasotto, MB, Szabo, I, Whitworth, AJ, Scorrano, L & Ziviani, E 2019, 'Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction', Life Science Alliance, vol. 2, no. 2, e201900392. https://doi.org/10.26508/lsa.201900392
Von Stockum S, Sanchez-Martinez A, Corrà S, Chakraborty J, Marchesan E, Locatello L et al. Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction. Life Science Alliance. 2019 Jan 1;2(2). e201900392. https://doi.org/10.26508/lsa.201900392
Von Stockum, Sophia ; Sanchez-Martinez, Alvaro ; Corrà, Samantha ; Chakraborty, Joy ; Marchesan, Elena ; Locatello, Lisa ; Rè, Caterina Da ; Cusumano, Paola ; Caicci, Federico ; Ferrari, Vanni ; Costa, Rodolfo ; Bubacco, Luigi ; Rasotto, Maria Berica ; Szabo, Ildiko ; Whitworth, Alexander J. ; Scorrano, Luca ; Ziviani, Elena. / Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction. In: Life Science Alliance. 2019 ; Vol. 2, No. 2.
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