TMEM59L is a newly identified brain-specific membrane-anchored protein with unknown functions. Herein we found that both TMEM59L and its homolog, TMEM59, are localized in Golgi and endosomes. However, in contrast to a ubiquitous and relatively stable temporal expression of TMEM59, TMEM59L expression was limited in neurons and increased during development. We also found that both TMEM59L and TMEM59 interacted with ATG5 and ATG16L1, and that overexpression of them triggered cell autophagy. However, overexpression of TMEM59L induced intrinsic caspase-dependent apoptosis more dramatically than TMEM59. In addition, downregulation of TMEM59L prevented neuronal cell death and caspase-3 activation caused by hydrogen peroxide insults and reduced the lipidation of LC3B. Finally, we found that AAV-mediated knockdown of TMEM59L in mice significantly ameliorated caspase-3 activation, increased mouse duration in the open arm during elevated plus maze test, reduced mouse immobility time during forced swim test, and enhanced mouse memory during Y-maze and Morris water maze tests. Together, our study indicates that TMEM59L is a pro-apoptotic neuronal protein involved in animal behaviors such as anxiety, depression, and memory, and that TMEM59L downregulation protects neurons against oxidative stress.
a SiO x -based anodes have attracted tremendous attention owing to their low cost, higher theoretical capacity than graphite and lower volume expansion than pure silicon. In this work, a simple and cost-effective two-step ball-milling method was proposed to fabricate Si/SiO x /C composites by using commercial SiO and graphite carbon as raw materials. The two-step ball-milling synthesis of the Si/SiO x /C composites can avoid the generation of an inert SiC phase and realize the uniform dispersion of Si/SiO x in graphite carbon, which offers good electrical conductivity and relieves the volume expansion of the Si/SiO x phase. Owing to the synergistic effect of the Si/SiO x phase and the graphite carbon, the typical Si/SiO x /C electrode exhibits a stable and high capacity of 726 mA h g À1 after 500 cycles at a current density of 0.1 A g À1 with a capacity retention of 82%. The two-step ball-milling preparation of the Si/SiO x /C composite provides a facile approach to fabricate high-performance SiO x -based anode materials.
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