Biology subjects

Karavaeva, I.

Publications and source records attributed to Karavaeva, I..

3 recordsLinked to original sources

bioRxiv2026

Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of interorganellar lipid cycling

Adipocyte lipid metabolism is coordinated by circadian rhythms, diet, and environmental temperature. Yet how these diverse signals are molecularly integrated remains unknown. Here we show that clock, diet, and temperature cues converge on the orphan mitochondrial transporter, SLC25A34, to orchestrate thermogenic cycling of lipid synthesis and oxidation. During sleep, the clock suppresses Slc25a34 transcription through REV-ERB. Waking, lipid-rich diets, or cold exposure abolish this repression, allowing lipolytic signals to stimulate Slc25a34 expression via PPAR. SLC25A34 then imports oxaloacetate into mitochondria to accelerate the export of substrates used for acetyl-CoA production in the cytosol. This feeds into cytosolic lipid synthesis and transcriptional induction of mitochondrial biogenesis, which collectively promote mitochondrial lipid oxidation. Thus, SLC25A34 confers circadian, dietary, and environmental control of thermogenic metabolism through interorganellar lipid cycling.

molecular biology↗

bioRxiv2024

Inheritance bias of deletion-harbouring mtDNA in yeast: the role of copy number and intracellular selection

Eukaryotic cells contain multiple copies of mitochondrial DNA (mtDNA) molecules that replicate independently. Cell mtDNA content and variability contributes to the overall cell fitness. During sexual reproduction, fungi usually inherit mtDNA from both parents, however, the distribution of the mtDNA in the progeny can be biased toward some mtDNA variants. For example, crossing Saccharomyces cerevisiae strain carrying wild type (rho+) mtDNA with the strain carrying mutant mtDNA variant with large deletion (rho-) can produce up to 99-100% of rho- diploid progeny. Two factors could contribute to this phenomenon. First, rho- cells may accumulate more copies of mtDNA molecules per cell than wild-type cells, making rho- mtDNA a prevalent mtDNA molecule in zygotes. This consequently leads to a high portion of rho - diploid cells in the offspring. Second, rho- mtDNA may have a competitive advantage within heteroplasmic cells, and therefore could displace rho+ mtDNA in a series of generations, regardless of their initial ratio. To assess the contribution of these factors, we investigated the genotypes and phenotypes of twenty two rho- yeast strains. We found that indeed rho- cells have a higher mtDNA copy number per cell than rho+ strains. Using an in silico modelling of mtDNA selection and random drift in heteroplasmic yeast cells, we assessed the intracellular fitness of mutant mtDNA variants. Our model indicates that both higher copy numbers and intracellular fitness advantage of the rho- mtDNA contribute to the biased inheritance of rho- mtDNA.

genetics↗

bioRxiv2019

Housing temperature influences exercise training adaptations in mice

Exercise training is a powerful means to combat metabolic pathologies. Mice are extensively used to describe the benefits of exercise, but mild cold stress induced by housing temperatures may confound translation to humans. Thermoneutral housing is a strategy to make mice more metabolically similar to humans but its effects on exercise adaptations are unknown. Using voluntary wheel running, we show that thermoneutral housing blunted exercise-induced improvements in insulin action in muscle and adipose tissue. Moreover, thermoneutrality reduced the effects of training on energy expenditure, body composition, muscle and adipose tissue protein expressions, and the gut microbiome. The majority of these thermoneutral-dependent training adaptations could not be ascribed to a lower voluntary running volume. Thus, we conclude that organismal adaptations to exercise training in mice critically depend upon housing temperature. Our findings underscore the importance of housing temperature as an important parameter in the design and interpretation of murine exercise studies.\n\nHighlightsO_LIHousing at 30{degrees}C blunts several adaptations to exercise training in mice\nC_LIO_LIExercise-sensitive protein induction is dampened at 30{degrees}C in skeletal muscle\nC_LIO_LI30{degrees}C-housing blunts training-induced increase in insulin-stimulated glucose uptake\nC_LIO_LIGlucose tolerance is not improved by voluntary exercise training at 30{degrees}C housing\nC_LIO_LIDecreased running in 30{degrees}C housing is not due to overheating\nC_LI\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/651588v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (68K):\norg.highwire.dtl.DTLVardef@1e5b6acorg.highwire.dtl.DTLVardef@3be37corg.highwire.dtl.DTLVardef@1d3febborg.highwire.dtl.DTLVardef@f8da30_HPS_FORMAT_FIGEXP M_FIG Graphical abstract\n\nC_FIG

physiology↗