De Lazzari 2022 Neurobiol Dis

From Bioblast
Publications in the MiPMap
De Lazzari F, Agostini F, Plotegher N, Sandre M, Greggio E, Megighian A, Bubacco L, Sandrelli F, Whitworth AJ, Bisaglia M (2022) DJ-1 promotes energy balance by regulating both mitochondrial and autophagic homeostasis.

Β» Neurobiol Dis 176:105941. PMID: 36473592 Open Access

De Lazzari Federica, Agostini Francesco,  Plotegher Nicoletta,  Sandre Michele,  Greggio Elisa, Megighian Aram, Bubacco Luigi,  Sandrelli Frederica,  Whitworth Alexander J,  Bisaglia Marco (2022) Neurobiol Dis

Abstract: The protein DJ-1 is mutated in rare familial forms of recessive Parkinson's disease and in parkinsonism accompanied by amyotrophic lateral sclerosis symptoms and dementia. DJ-1 is considered a multitasking protein able to confer protection under various conditions of stress. However, the precise cellular function still remains elusive. In the present work, we evaluated fruit flies lacking the expression of the DJ-1 homolog dj-1Ξ² as compared to control aged-matched individuals. Behavioral evaluations included lifespan, locomotion in an open field arena, sensitivity to oxidative insults, and resistance to starvation. Molecular analyses were carried out by analyzing the mitochondrial morphology and functionality, and the autophagic response. We demonstrated that dj-1Ξ² null mutant flies are hypoactive and display higher sensitivity to oxidative insults and food deprivation. Analysis of mitochondrial homeostasis revealed that loss of dj-1Ξ² leads to larger and more circular mitochondria, characterized by impaired complex-I-linked respiration while preserving ATP production capacity. Additionally, dj-1Ξ² null mutant flies present an impaired autophagic response, which is suppressed by treatment with the antioxidant molecule N-Acetyl-L-Cysteine. Overall, our data point to a mechanism whereby DJ-1 plays a critical role in the maintenance of energy homeostasis, by sustaining mitochondrial homeostasis and affecting the autophagic flux through the maintenance of the cellular redox state. In light of the involvement of DJ-1 in neurodegenerative diseases and considering that neurons are highly energy-demanding cells, particularly sensitive to redox stress, our study sheds light on a key role of DJ-1 in the maintenance of cellular homeostasis. β€’ Keywords: Autophagy, DJ-1, Energy balance, Mitochondria, Redox homeostasis β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: UK Cambridge Whitworth A

Labels: MiParea: Respiration, mt-Structure;fission;fusion  Pathology: Neurodegenerative, Parkinson's 

Organism: Drosophila 

Preparation: Homogenate 

Coupling state: OXPHOS  Pathway: N, S  HRR: Oxygraph-2k 


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