bims-apauto 2021-10-03 papers

Issue of 2021–10–03
three papers selected by
Su Hyun Lee, Seoul National University

FASEB J. 2021 Oct;35(10): e21848

The role of lysosomal membrane proteins in glucose and lipid metabolism.

Jing Gu, Mengya Geng, Mengxiang Qi, Lizhuo Wang, Yao Zhang, Jialin Gao.

Lysosomes have long been regarded as the "garbage dump" of the cell. More recently, however, researchers have revealed novel roles for lysosomal membranes in autophagy, ion transport, nutrition sensing, and membrane fusion and repair. With active research into lysosomal membrane proteins (LMP), increasing evidence has become available showing that LMPs are inextricably linked to glucose and lipid metabolism, and this relationship represents mutual influence and regulation. In this review, we summarize the roles of LMPs in relation to glucose and lipid metabolism, and describe their roles in glucose transport, glycolysis, cholesterol transport, and lipophagy. The role of transport proteins can be traced back to the original discoveries of GLUT8, NPC1, and NPC2, which were all found to have significant roles in the pathways involved in glucose and lipid metabolism. CLC-5 and SIDT2-knockout animals show serious phenotypic disorders of metabolism, and V-ATPase and LAMP-2 have been found to interact with proteins related to glucose and lipid metabolism. These findings all emphasize the critical role of LMPs in glycolipid metabolism and help to strengthen our understanding of the independent and close relationship between LMPs and glycolipid metabolism.

Keywords: glucose metabolism; lipid metabolism; lysosomal membrane protein

DOI: https://doi.org/10.1096/fj.202002602R

Hepatology. 2021 Sep 28.

ER stress promotes HBV production by enhancing utilization of the autophagosome- multivesicular body axis.

Xueyu Wang, Zhiqiang Wei, Bin Cheng, Jia Li, Yulin He, Tingyu Lan, Thekla Kemper, Yong Lin, Bin Jiang, Yongfang Jiang, Zhongji Meng, Mengji Lu.

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection has been reported to trigger endoplasmic reticulum (ER) stress and initiate autophagy. However, how ER stress and autophagy influence HBV production remains elusive. Here, we studied the effect of tunicamycin (TM), an N-glycosylation inhibitor and ER stress inducer, on HBV replication and secretion, and examined the underlying mechanisms.
APPROACH & RESULTS: PDI (an ER marker), LC3 (an autophagosome marker) and p62 (a typical cargo for autophagic degradation) expression were tested in the liver tissues of patients with chronic HBV infection and hepatoma cell lines. The role of TM treatment in HBV production and trafficking was examined in hepatoma cell lines. TM treatment that mimics HBV infection triggered ER stress and increased autophagosome formation, resulting in enhanced HBV replication and the secretion of subviral particles (SVPs) and naked capsids. Additionally, TM reduced the number of early endosomes and HBV surface antigen (HBsAg) localization in this compartment, causing HBsAg/SVPs accumulate in the ER. Thus, TM-induced autophagosome formation serves as an alternative pathway for HBsAg/SVPs trafficking. Importantly, TM inhibited autophagosome-lysosome fusion, accompanied by enhanced autophagosome-late endosome/multivesicular body (MVB) fusion to release HBsAg/SVPs through or along with exosome release. Notably, TM treatment inhibited the HBsAg glycosylation, resulting in impairment of the HBV virions envelopment and secretion, but it was not critical for HBsAg/SVPs trafficking in our cell systems.
CONCLUSIONS: TM-induced ER stress and autophagic flux promoted HBV replication and the release of SVPs and naked capsids through the autophagosome-late endosome/MVB axis.

Keywords: Hepatitis B virus; autophagosome; multivesicular bodies/MVBs; vesicular trafficking

DOI: https://doi.org/10.1002/hep.32178

EMBO J. 2021 Sep 28. e109575

AMPK CA(R)Sts a new light on amino acid sensing.

Kristin K Brown.

AMP-activated protein kinase (AMPK) is recognized as a critical regulator of cellular energy metabolism impacted by AMP/ATP and ADP/ATP ratios, or glucose- and fatty acid-derived metabolites. However, its ability to sense alterations in amino acid levels is poorly understood. Recent work by Yuan et al (2021) identifies a novel mechanism of AMPK regulation responsive to changes in availability of the sulfur-containing amino acid cysteine.

DOI: https://doi.org/10.15252/embj.2021109575