Vol.45, No.4, 2021, pp.963-970, doi:10.32604/biocell.2021.015297
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ARTICLE
SOD1G93A Induces a Unique PSAP-Dependent Mitochondrial Apoptosis Pathway via Bax–Bak Interaction
  • HAN NIU1,#, XIN CHEN1,#, XUEQI FU1, JINGTIAN ZHANG1, GUODONG LI4, YUXIANG WANG1, JIAYUE SONG1, XUETING MA1, CHEN HU5, XUEMIN XU3, FUQIANG ZHANG2,*, LINLIN ZENG1,*
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
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, SOD1G93A 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 SOD1G93A-induced apoptosis and demonstrated that the overexpression of SOD1G93A, but not wtSOD1, induced PARP cleavage, caspase-3 activation, cytochrome c release, and Bax translocation. PSAP, Bax, and Bak were necessary for SOD1G93A-induced apoptosis, as silencing PSAP inhibited SOD1G93A-mediated cell death that was dependent on Bax–Bak interaction.
Keywords
ALS; Bax; Mitochondria; PSAP; SOD1G93A
Cite This Article
NIU, H., CHEN, X., FU, X., ZHANG, J., LI, G. et al. (2021). SOD1G93A Induces a Unique PSAP-Dependent Mitochondrial Apoptosis Pathway via Bax–Bak Interaction. BIOCELL, 45(4), 963–970.
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