An RDH-Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase.

The size of lipid droplets varies greatly in vivo and is determined by both intrinsic and extrinsic factors. From an RNAi screen in Drosophila, we found that knocking down subunits of COP9 signalosome (CSN) results in enlarged lipid droplets under high-fat, but not normal, conditions. We identified CG2064, a retinol dehydrogenase (RDH) homolog, as the proteasomal degradation target of CSN in regulating lipid droplet size. RDH/CG2064 interacts with the lipid droplet-resident protein Plin2 and the RDH/CG2064-Plin2 axis acts to reduce the overall level and lipid droplet localization of Bmm/ATGL lipase. This axis is important for larval survival under prolonged starvation. Thus, we discovered an RDH-Plin2 axis modulates lipid droplet size.

Rationally Tailoring Chiral Molecules to Minimize Interfacial Energy Loss Enables Efficient and Stable Perovskite Solar Cells Using Vacuum Flash Technology.

Facing the defects and energy barrier at the interface of perovskite solar cells, we propose a chiral molecule engineering strategy to simultaneously heal interfacial defects and regulate interfacial energy band alignment. S-ibuprofen (S-IBU), R-ibuprofen (R-IBU), and racemic ibuprofen (rac-IBU) are used to post-treat perovskite films. rac-IBU molecules possess the strongest anchoring on the surface of perovskites among all chiral molecules, translating into the best defect passivation effect. The hydrophobic isobutyl group and benzene ring could increase the film moisture resistance ability. Due to reduced interfacial defects and interfacial energy barrier, rac-IBU enables efficient devices with a maximum efficiency exceeding 24% based on vacuum flash technology without antisolvents. The encapsulated rac-IBU-modified device could maintain 90% of its initial performance after 1040 h of continuous maximum power point tracking. This work provides a feasible route to minimize interfacial nonradiative recombination losses by controlling spatial conformation via rational chiral molecule engineering.

N-end Rule-Mediated Proteasomal Degradation of ATGL Promotes Lipid Storage.

Cellular lipid storage is regulated by the balance of lipogenesis and lipolysis. The rate-limiting triglyceride hydrolase ATGL (desnutrin/PNPLA2) is critical for lipolysis. The control of ATGL transcription, localization, and activation has been intensively studied, while regulation of the protein stability of ATGL is much less explored. In this study, we showed that the protein stability of ATGL is regulated by the N-end rule in cultured cells and in mice. The N-end rule E3 ligases UBR1 and UBR2 reduce the level of ATGL and affect lipid storage. The N-end rule-resistant ATGL(F2A) mutant, in which the N-terminal phenylalanine (F) of ATGL is substituted by alanine (A), has increased protein stability and enhanced lipolysis activity. ATGLF2A/F2A knock-in mice are protected against high-fat diet (HFD)-induced obesity, hepatic steatosis, and insulin resistance. Hepatic knockdown of Ubr1 attenuates HFD-induced hepatic steatosis by enhancing the ATGL level. Finally, the protein levels of UBR1 and ATGL are negatively correlated in the adipose tissue of obese mice. Our study reveals N-end rule-mediated proteasomal regulation of ATGL, a finding that may potentially be beneficial for treatment of obesity.