Open Access

ARTICLE

SOD1^G93A Induces a Unique PSAP-Dependent Mitochondrial Apoptosis Pathway via Bax–Bak Interaction

HAN NIU^1,#, XIN CHEN^1,#, XUEQI FU¹, JINGTIAN ZHANG¹, GUODONG LI⁴, YUXIANG WANG¹, JIAYUE SONG¹, XUETING MA¹, CHEN HU⁵, XUEMIN XU³, FUQIANG ZHANG^2,*, LINLIN ZENG^1,*

1 Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, Jilin University, Changchun, 130012, China
2 Scientific Research Centre of China-Japan Union Hospital, Jilin University, Changchun, 130033, China
3 Department of Biology, College of Arts and Sciences, University of Texas of the Permian Basin, Odessa, TX 79762, USA
4 Department of General Surgery, The Second Hospital of Jilin University, Changchun, 130041, China
5 School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China

BIOCELL 2021, 45(4), 963-970. https://doi.org/10.32604/biocell.2021.015297

Received 08 December 2020; Accepted 18 February 2021; Issue published 22 April 2021

Abstract

Amyotrophic lateral syndrome (ALS) is a progressive degenerative disorder characterized by motor neuron death and axon degeneration. Mitochondrial dysfunction plays a key role in the pathogenesis of ALS, the mechanism of which remains poorly understood. The B-cell lymphoma-2 (Bcl-2) family of proteins that control and mediate mitochondrial function and apoptosis, including the pro-apoptotic members Bcl2-Associated X (Bax), are involved in ALS development. The death receptor 6 (DR6) regulates motor neuron death in ALS, and DR6 antibodies can prevent axon degeneration and motor neuron damage by blocking DR6. Previous studies demonstrated that PSAP localized to mitochondria and was required for DR6-induced apoptosis. In this study, SOD1^G93A was transfected into the motor neuron cell line NSC-34 to serve as an ALS cell model in vitro. The data assessed the role of PSAP in SOD1^G93A-induced apoptosis and demonstrated that the overexpression of SOD1^G93A, but not wtSOD1, induced PARP cleavage, caspase-3 activation, cytochrome c release, and Bax translocation. PSAP, Bax, and Bak were necessary for SOD1^G93A-induced apoptosis, as silencing PSAP inhibited SOD1^G93A-mediated cell death that was dependent on Bax–Bak interaction.

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