α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line

Risiglione, Pierpaolo; Cubisino, Salvatore Antonio Maria; Lipari, Cristiana Lucia Rita; De Pinto, Vito; Messina, Angela; Magrì, Andrea

doi:10.3390/life12060894

Open AccessArticle

α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line

by

Pierpaolo Risiglione

¹,

Salvatore Antonio Maria Cubisino

¹,

Cristiana Lucia Rita Lipari

¹,

Vito De Pinto

^1,2

,

Angela Messina

^2,3,*

and

Andrea Magrì

^2,3,*

¹

Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 64, 95125 Catania, Italy

²

we.MitoBiotech S.R.L., Corso Italia 172, 95125 Catania, Italy

³

Department of Biological, Geological and Environmental Sciences, University of Catania, Via S. Sofia 64, 95125 Catania, Italy

^*

Authors to whom correspondence should be addressed.

Life 2022, 12(6), 894; https://doi.org/10.3390/life12060894

Submission received: 20 May 2022 / Revised: 14 June 2022 / Accepted: 14 June 2022 / Published: 15 June 2022

(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)

Download

Browse Figures

Versions Notes

Abstract

α-synuclein (αSyn) is a small neuronal protein whose accumulation correlates with Parkinson’s disease. αSyn A53T mutant impairs mitochondrial functions by affecting substrate import within the organelle, activity of complex I and the maximal respiratory capacity. However, the precise mechanism initiating the bioenergetic dysfunction is not clearly understood yet. By overexpressing αSyn A53T in SH-SY5Y cells, we investigated the specific changes in the mitochondrial respiratory profile using High-Resolution Respirometry. We found that αSyn A53T increases dissipative fluxes across the intermembrane mitochondrial space: this does not compromise the oxygen flows devoted to ATP production while it reduces the bioenergetic excess capacity of mitochondria, providing a possible explanation of the increased cell susceptibility observed in the presence of further stress stimuli.

Keywords: αSyn; mitochondrial dysfunction; Parkinson’s disease; high-resolution respirometry

Share and Cite

MDPI and ACS Style

Risiglione, P.; Cubisino, S.A.M.; Lipari, C.L.R.; De Pinto, V.; Messina, A.; Magrì, A. α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line. Life 2022, 12, 894. https://doi.org/10.3390/life12060894

AMA Style

Risiglione P, Cubisino SAM, Lipari CLR, De Pinto V, Messina A, Magrì A. α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line. Life. 2022; 12(6):894. https://doi.org/10.3390/life12060894

Chicago/Turabian Style

Risiglione, Pierpaolo, Salvatore Antonio Maria Cubisino, Cristiana Lucia Rita Lipari, Vito De Pinto, Angela Messina, and Andrea Magrì. 2022. "α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line" Life 12, no. 6: 894. https://doi.org/10.3390/life12060894

APA Style

Risiglione, P., Cubisino, S. A. M., Lipari, C. L. R., De Pinto, V., Messina, A., & Magrì, A. (2022). α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line. Life, 12(6), 894. https://doi.org/10.3390/life12060894

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI