SYNJ2BP ameliorates intervertebral disc degeneration by facilitating mitochondria-associated endoplasmic reticulum membrane formation and mitochondrial Zn < sup > 2+ < /sup > homeostasis

Free Radic Biol Med. 2023 Dec 27;212:220-233. doi: 10.1016/j.freeradbiomed.2023.12.028. Online ahead of print.ABSTRACTNucleus pulposus (NP) cell function-loss is one main contributor during intervertebral disc degeneration (IDD) progression. Both mitochondria and endoplasmic reticulum (ER) play vital roles in sustaining NP cell homeostasis, while the precise function of ER-mitochondria tethering and cross talk in IDD remain to be clarified. Here, we demonstrated that a notable disruption of mitochondria-associated ER membrane (MAM) was identified in degenerated discs and TBHP-induced NP cells, accompanied by mitochondrial Zn2+ overload and NP cell senescence. Importantly, experimental coupling of MAM contacts by MFN2, a critical regulator of MAM formation, could enhance NLRX1-SLC39A7 complex formation and mitochondrial Zn2+ homeostasis. Further using the sequencing data from TBHP-induced degenerative model of NP cells, combining the reported MAM proteomes, we demonstrated that SYNJ2BP loss was one critical pathological characteristic of NP cell senescence and IDD progression, which showed close relationship with MAM disruption. Overexpression of SYNJ2BP could facilitate MAM contact organization and NLRX1-SLC39A7 complex formation, thus promoted mitochondrial Zn2+ homeostasis, NP cell proliferation and intervertebral disc rejuvenation. Collectively, our present study revealed a critical role of SYNJ2BP in maintaining mitochondrial Zn2+ homeostasis in NP cells during IDD progre...

Source: Free Radical Biology and Medicine - December 29, 2023 Category: Biology Authors: Yu Song Wen Geng Dingchao Zhu Huaizhen Liang Zhi Du Bide Tong Kun Wang Shuai Li Yong Gao Xiaobo Feng Zhiwei Liao Rongcheng Mei Cao Yang Source Type: research