Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.03.24.003442

UCP3 plays a complementary role to UCP1 in brown adipose tissue mitochondrial bioenergetics

Riley, C. L.·Mills, E.
View original source ↗Export metadata ↓

Abstract

Mitochondrial uncoupling protein 3 (UCP3) plays a complementary role in uncoupling protein 1 (UCP1)-dependent uncoupling in mammalian thermogenesis. Using mouse strains that lack UCP1 or UCP3, plus a UCP1/UCP3 double knockout, we have previously demonstrated that UCP3 is necessary for sustained heat production. However, how and where UCP3 is essential for heat production remains unknown. Here we use brown adipocyte mitochondria from mice lacking UCP1, UCP3, or UCP1 plus UCP3 (double knockout) we found that in the absence of UCP1, UCP3 does not act as a free fatty acid-inducible uncoupling protein; however, UCP3 is necessary for maximal GDP-sensitive respiration. We additionally confirm that the loss of UCP1 is a dominant regulator of mitochondrial respiratory chain activity, assembly, and composition in brown adipose tissue. Our data suggest without UCP1, brown adipose tissue is not a significant source of heat production, and that UCP3-dependent heat generation serves a regulatory function outside of adipose tissues. Together these findings suggest that in brown adipose tissue, UCP3s thermogenic function is independent of its role as a bona fide uncoupling protein.

Explore related subjects

biochemistryPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Riley, C. L., Mills, E.. 2020-03-25. UCP3 plays a complementary role to UCP1 in brown adipose tissue mitochondrial bioenergetics. https://doi.org/10.1101/2020.03.24.003442

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Structure of influenza D virus NS1 reveals a novel Zn-binding site and ssRNA-binding activity

Influenza D virus (IDV) is an emerging pathogen associated with bovine respiratory disease and has potential for zoonotic transmission. Although nonstructural protein 1 (NS1) is a major virulence factor in influenza A and B viruses, the structure and function of IDV NS1 remain poorly defined. Here, we determined crystal structures of the IDV NS1 N-terminal RNA-binding domain (NTD) and C-terminal effector domain (CTD). The NTD retains the conserved homodimeric six-helix fold, whereas the CTD adopts a distinct architecture containing a novel Zn2+-binding site. IDV NS1 CTD preferentially binds single-stranded RNA, and mutagenesis identified lysine and arginine residues critical for this activity. Single-residue substitutions disrupting either the Zn2+-binding site or RNA-binding interface prevented recovery of infectious recombinant IDV. These findings reveal distinct structural and functional features of IDV NS1 and establish the importance of CTD integrity for viral replication. Conservation of key CTD residues in influenza C virus NS1 suggests shared structural features that distinguish influenza C and D virus NS1 proteins from their influenza A and B counterparts.

biochemistry↗
bioRxiv2026

QC-espresso: Brewing quality in proteomics

Data-independent acquisition (DIA) proteomics has become a standard approach for high-throughput proteomics, with DIA-NN emerging as one of the most widely adopted data-analysis platforms. However, despite the detailed information available in DIA-NN output reports, proteomics researchers may lack a streamlined and reproducible approach for assessing acquisition quality, identification consistency, and quantitative reliability across experiments. QC-espresso addresses this need through an automated, report-centered quality-control workflow implemented in R and Quarto. The tool processes a DIA-NN report.parquet file together with the corresponding FASTA database and generates a structured HTML report containing plots, run-level statistics, and exportable summary tables. Application to three experimental datasets allowed the visualization of lower identification depth related to high contaminant content; a chromatographic transition accompanied by altered retention-time and peak-width behavior; and the co-occurrence of systematic mass-error bias with changes in precursor- and protein-level quantitative-quality metrics. QC-espresso can be executed directly in R or through a portable Windows distribution with a graphical launcher, with both modes using the same analytical modules and report-generation workflow. The resulting report provides a consistent record for local inspection and troubleshooting of quality-control metrics within individual DIA proteomics experiments. QC-espresso is freely available at https://github.com/lanfredig/QC-espresso_DIA.

biochemistry↗
bioRxiv2026

Molecular crowding differentially regulates magnetic field-dependent fluorescence, recovery kinetics, and photostability of the magnetosensitive protein MagLOV2

Macromolecular crowding and solvent composition can alter protein conformation, diffusion, hydration, and cofactor photophysics, yet their influence on magnetically sensitive flavoproteins is poorly understood. We tested seven molecular environments in MagLOV2-overexpressing Escherichia coli lysate using a custom-built, high-intensity magnetofluorescence platform. Five-point concentration series of Dextran 70, Ficoll PM70, PEG6000, PEG3350, glycerol, ethylene glycol, and bovine serum albumin (BSA) were measured at 22 mT under continuous 6.12 W/cm2 blue-light excitation. Dextran 70, Ficoll PM70, and PEG6000 progressively attenuated the negative magnetic field effect (MFE), whereas PEG3350 shifted toward mild enhancement at higher concentrations. Glycerol and ethylene glycol enhanced the negative MFE despite producing the strongest slowing of recovery upon the field being switched off (OFF-recovery), while BSA modestly enhanced MFE and accelerated OFF-recovery. Across 105 treatment cuvettes, the change in MFE was not globally correlated with changes in the OFF-recovery time constant (r = -0.07, p = 0.449). The initial pre-field illumination period revealed a second phenotype: Dextran and Ficoll increased late fluorescence loss, whereas glycerol and BSA were photoprotective. Pre-field fluorescence loss correlated moderately with MFE change across the full dataset (r = 0.474, p = 3.28 x 10-7) but not consistently within crowder classes. These findings show that MagLOV2 spin-dependent magnetofluorescence is shaped by crowder chemistry, polymer size, solvent environment, recovery kinetics, and photostability rather than by a single generic crowding or viscosity mechanism.

biochemistry↗