Staphylococcal nuclease domain-containing protein 1 (SND1) is an evolutionarily conserved multifunctional protein that functions mainly in the nucleus and cytoplasm. However, whether SND1 regulates cellular activity through mitochondrial-related functions remains unclear. Herein, we demonstrate that SND1 is localized to mitochondria to promote phosphoglycerate mutase 5 (PGAM5)-mediated mitophagy. We find that SND1 is present in mitochondria based on mass spectrometry data and verified this phenomenon in different liver cancer cell types by performing organelle subcellular isolation. Specifically, The N-terminal amino acids 1-63 of SND1 serve as a mitochondrial targeting sequence (MTS), and the translocase of outer membrane 70 (TOM 70) promotes the import of SND1 into mitochondria. By immunoprecipitation-mass spectrometry (IP-MS), we find that SND1 interacts with PGAM5 in mitochondria and is crucial for the binding of PGAM5 to dynamin-related protein 1 (DRP1). Importantly, we demonstrate that PGAM5 and SND1-MTS are required for SND1-mediated mitophagy under FCCP and glucose deprivation treatment as well as for SND1-mediated cell proliferation and tumor growth both in vitro and in vivo. Aberrant expression of SND1 and PGAM5 predicts poor outcomes in hepatocellular carcinoma (HCC) patients. Taken together, these findings establish a previously unappreciated role of SND1 and the association of mitochondrion-localized SND1 with PGAM5 in mitophagy and tumor progression.
4H-SiC gate turn-off (GTO) thyristor offers extraordinary advantages over its counterparts in handling ultra-high voltage electric power conversion applications because of its relatively low forward voltage drop at high conduction current density. Besides, though the SiC thyristors never suffer from long carrier liftime induced large switching loss like Si thyristors, the peak temperature rise rather than dynamic avalanche breakdown is blamed for the safe operation area (SOA) failure, making further reduction of power loss in SiC GTOs even more important. In this paper, a 20 kV SiC GTO with direct carrier extraction access to its drift region (DA-GTO) is investigated to explore the benefit this structure could bring for SiC thyristors, namely achieving smaller switching loss and/or potential larger SOA with slight sacrifice in forward voltage drop at high current. The structure is formed by interleaved P + ion implantation into part of the thin N-injector layer based on conventional 20 kV SiC GTO. The SiC DA-GTO operates in BJT mode at low current, and in GTO mode with low forward voltage drop at high current. During turn-off process, it offers a direct current path to quickly sweep out the excess carriers in the P-drift region, thus speeds up the turn-off process and decreases the turn-off loss. Simulation results show that its turn-off loss reduces by 37.4%, contributing to 12.6% reduction in total power loss, compared with SiC GTO. Therefore, SiC DA-GTO is a very promising choice for next-generation power conversion systems.
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