High impact information on SLC25A27

• We recently reported the identification of a brain-specific mitochondrial uncoupling protein homologue, UCP4 [1].
• These findings are consistent with the notion that UCP4 and UCP5 may be involved in tissue-specific thermoregulation and metabolic changes associated with nutritional status [1].
• Here we show that UCP4, a neuronal UCP, influences store-operated Ca(2+) entry, a process in which depletion of endoplasmic reticulum Ca(2+) stores triggers Ca(2+) influx through plasma membrane "store-operated" channels [2].
• Mitochondrial Uncoupling Protein-4 Regulates Calcium Homeostasis and Sensitivity to Store Depletion-induced Apoptosis in Neural Cells [2].
• The elevations of cytoplasmic and intramitochondrial Ca(2+) concentrations and mitochondrial oxidative stress induced by thapsigargin were attenuated in cells expressing UCP4 [2].

Biological context of SLC25A27

• Speculations on UCP4 participation in apoptosis are thus supported by its early phylogenetic occurrence [3].
• These findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolism in the brain [4].
• UCP4 maps to human chromosome 6p11.2-q12 [4].
• UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells [4].
• The expression of UCP-4 is itself regulated by changes in energy metabolism [5].

Anatomical context of SLC25A27

• Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammalian cells reduces mitochondrial membrane potential [4].
• PC12 neural cells expressing human UCP4 exhibit reduced Ca(2+) entry in response to thapsigargin-induced endoplasmic reticulum Ca(2+) store depletion [2].
• However, the effect of UCP4 on adipocytes is unclear [6].
• We previously showed that uncoupling protein 4 (UCP4) is differentially expressed in omental adipose tissue in diet-induced obese and normal rats [6].
• In this work, we established a stable preadipocyte cell line overexpressing UCP4 to observe the direct effect of UCP4 on adipocytes [6].

Associations of SLC25A27 with chemical compounds

• Reduced Ca(2+)-dependent cytosolic phospholipase A2 activation and oxidative metabolism of arachidonic acid also contributed to the stabilization of mitochondrial function in cells expressing human UCP4 [2].
• UCP4 modulates neuronal energy metabolism by increasing glucose uptake and shifting the mode of ATP production from mitochondrial respiration to glycolysis, thereby maintaining cellular ATP levels [7].

Other interactions of SLC25A27

• This suggests that UCP4 represents the ancestral UCP from which other mammalian and plant UCPs diverged [3].
• Protein sequence analyses showed that UCP4 is most related to UCP3 and possesses features characteristic of mitochondrial transporter proteins [4].
• UCP2 and UCP4 expression were unaffected by UCP5 knockdown [8].
• Phylogenetic analysis indicates that there are at least three clades of UCPs in invertebrates, which are closely related to vertebrate UCP1-3, UCP4, and UCP5, respectively, and shows early evolutionary divergence of UCPs, which pre-dates the divergence of protostomes and deuterostomes [9].
• This study refutes the hypothesis of Hanak and Jezek (2001) that UCP4 is an ancestral form for all UCPs, and shows early evolutionary diversification of this protein family, which corresponds to their proposed functional diversity in regulation of proton leak, antioxidant defense and apoptosis [9].

Analytical, diagnostic and therapeutic context of SLC25A27

• UCP4-mRNA expression is increased in neurons exposed to cold temperatures and in brain cells of rats maintained on caloric restriction, suggesting a role for UCP4 in the previously reported antiageing and neuroprotective effects of caloric restriction [7].

References