Biology subjects

Paulsson, E.

Publications and source records attributed to Paulsson, E..

3 recordsLinked to original sources

bioRxiv2026

Adaptation of white adipocytes to cooler temperatures: impacts on energy metabolism and protein acetylation

Adipocytes throughout the body reside in distinct thermal environments. Visceral adipocytes within the body core are maintained near 37 {degrees}C, whereas those in bone marrow, subcutaneous, and dermal depots occupy cooler regions within the peripheral shell. While brown and beige adipocyte responses to cold stress are well characterized, much less is known about how white adipocytes adapt to moderately reduced temperatures below 37 {degrees}C. Our recent work revealed that cultured adipocytes exposed to 31 {degrees}C, a temperature representative of distal adipose regions, exhibit enhanced mitochondrial function, including increased substrate oxidation and ATP turnover, yet the mechanisms underlying this upregulation remain unclear. Here we show that adaptation to cool temperatures leads to a widespread decrease in protein acetylation in both undifferentiated and differentiated adipocytes, independent of nutrient status, and that this change is readily reversible upon rewarming. Subcellular fractionation and immunoblotting demonstrate that the hypoacetylation coincides with a compartment-specific enrichment of acetylated proteins within mitochondria, indicating selective remodeling of the mitochondrial acetylome. Transcriptomic and biochemical analyses reveal that these temperature-dependent changes occur without alterations in acetyltransferase or deacetylase expression, NAD concentration, or acetyl-CoA availability, suggesting regulation through alternative mechanisms affecting acetyl-CoA flux or enzyme activity. Integrative acetyl-proteomic and metabolomic profiling identifies mitochondrial enzymes, including serine hydroxymethyltransferase 2 (SHMT2) and propionyl-CoA carboxylase (PCCA), whose acetylation correlates closely with changes in associated metabolite pools. Together, these findings establish physiologically relevant cooling as a cell-autonomous regulator of mitochondrial protein acetylation and metabolic adaptation in adipocytes.

cell biology↗

bioRxiv2025

Evolutionary trajectories determine the feasibility of collateral sensitivity based antibiotic treatment strategies in critical bacterial pathogens

The rise of antibiotic resistance among pathogenic bacteria necessitates innovative therapeutic strategies. A promising technique is the use of collateral sensitivity where resistance to one antibiotic increases susceptibility to another. In this study, we explored the clinical relevance of collateral sensitivity through experimental evolution and genetic engineering in six critical bacterial pathogens using 23 distinct antibiotics. Our in-depth analysis of Escherichia coli showed that clinically relevant resistance mutations did not confer collateral sensitivity to the tested antibiotics. We were able to identify at least three new classes of ciprofloxacin-resistance mutations that cause collateral sensitivity to multiple antibiotics. However, these mutations incur significant fitness costs and are absent in ciprofloxacin-resistant clinical isolates. Our further analysis showed that the development of collateral effects differed significantly between the tested species. Most species showed development of collateral sensitivity to gentamicin during ciprofloxacin-resistance evolution but Acinetobacter baumanii developed collateral resistance instead. Overall, Pseudomonas aeruginosa showed the most consistent development of collateral sensitivity among the tested species, highlighting it as a promising candidate for the use of collateral-sensitivity-based treatment strategies. Our findings provide insights into the potential of collateral sensitivity as a therapeutic strategy and contribute to the development of more effective antibiotic treatment regimens.

microbiology↗

bioRxiv2023

SCD1 and monounsaturated lipids are required for autophagy and survival of adipocytes

Exposure of adipocytes to cool temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (SCD1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. In this study, we employed Scd1 knockout cells and mouse models, along with pharmacological SCD1 inhibition, to investigate further the roles of SCD1 in adipocytes. Our study reveals that production of monounsaturated lipids by SCD1 is necessary for fusion of autophagosomes to lysosomes and that with a SCD1-deficiency, autophagosomes accumulate. In addition, SCD1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of SCD1-deficient adipocytes. Taken together, our results demonstrate that in vitro inhibition of SCD1 in adipocytes leads to autophagy-dependent cell death, and in vivo depletion leads to loss of bone marrow adipocytes.

molecular biology↗