BMCP1: a mitochondrial uncoupling protein in neurons which regulates mitochondrial function and oxidant production

Abstract

Outside the nervous system, members of the mitochondrial uncoupling protein (UCP) family have been proposed to contribute to control of body temperature and energy metabolism, and regulation of mitochondrial production of reactive oxygen species (ROS). However, the function of brain mitochondrial carrier protein 1 (BMCP1), which is highly expressed in brain, remains to be determined. To study BMCP1 expression and function in the nervous system, a high-af®nity antibody to BMCP1 was generated and used to analyze tissue expression of BMCP1 protein in mouse. BMCP1 protein was highly expressed in heart and kidney, but not liver or lung. In the nervous system, BMCP1 was present in cortex, basal ganglia, substantia nigra, cerebellum, and spinal cord. Both BMCP1 mRNA and protein expression was almost exclusively neuronal. To study the effect of BMCP1 expression on mitochondrial function, neuronal (GT1-1) cell lines with stable overexpression of BMCP1 were generated. Transfected cells had higher State 4 respiration and lower mitochondrial membrane potential (c m ), consistent with greater mitochondrial uncoupling. BMCP1 expression also decreased mitochondrial production of ROS. These data suggest that BMCP1 can modify mitochondrial respiratory ef®ciency and mitochondrial oxidant production, and raise the possibility that BMCP1 might alter the vulnerability of brain to both acute injury and to neurodegenerative conditions.

Temperature-dependent effects of cadmium and purine nucleotides on mitochondrial aconitase from a marine ectotherm,Crassostrea virginica: a role of temperature in oxidative stress and allosteric enzyme regulation

“…Two other oyster UCP homologs found in this study (UCP4 and UCP5), are closely related to mammalian UCP4 and UCP5, respectively. The functions of these UCPs are less well understood; although they have been suggested to play a role in antioxidant protection in brain and nervous tissues (Kim-Han et al, 2001;Haguenauer et al, 2005;Andrews et al, 2005), direct evidence for this is lacking and there is no general consensus as to their physiological function.…”

Identification and characterization of uncoupling protein 4 in fat body and muscle mitochondria from the cockroach Gromphadorhina cocquereliana

“…Mammalian UCP4 is exclusively expressed in different regions of the brain and spinal cord (Mao et al 1999;Smorodchenko et al 2009). UCP5 expression is highly enriched in the mammalian nervous system and is located exclusively in neurons (Sanchis et al 1998;Yu et al 2000;Kim-Han et al 2001). The evolution of UCP isoforms is under debate.…”

Mitochondrial Uncoupling Proteins in the Brain: Their Structure, Function and Physiological Roles [Beyindeki Mitokondriyal Eslesme Bozucu Proteinler: Yapisi, Islevi ve Fizyolojik Rolleri]

“…Farklı vücut dokularında dağılım gösteren bu protein grubunun 5 üyesi vardır. Kahverengi yağ dokuya özgü UCP1, vücut sıcaklığının korunmasında (titremesiz termogenez) ve yağ dokusu içerisinde depolanmış enerjinin kullanılmasında görev alır [11,12]. UCP2; dalak, pankreas adacık hücreleri, akciğer, mide, beyaz yağ doku, beyin ve periferal nöronların arka kök gangliyonlarında eksprese edilir [11][12][13][14][15].…”

“…Kahverengi yağ dokuya özgü UCP1, vücut sıcaklığının korunmasında (titremesiz termogenez) ve yağ dokusu içerisinde depolanmış enerjinin kullanılmasında görev alır [11,12]. UCP2; dalak, pankreas adacık hücreleri, akciğer, mide, beyaz yağ doku, beyin ve periferal nöronların arka kök gangliyonlarında eksprese edilir [11][12][13][14][15]. UCP3 öncelikle iskelet kasında olmak üzere az miktarda sinir hücrelerinde tespit edilmiştir [12,15,16].…”

“…UCP2; dalak, pankreas adacık hücreleri, akciğer, mide, beyaz yağ doku, beyin ve periferal nöronların arka kök gangliyonlarında eksprese edilir [11][12][13][14][15]. UCP3 öncelikle iskelet kasında olmak üzere az miktarda sinir hücrelerinde tespit edilmiştir [12,15,16]. Yapılan çalışmalar ile UCP4 ve UCP5'in (BMCP1; Beyin mitokondriyal taşıyıcı protein-1 olarak da bilinir) merkezi sinir sisteminde yüksek düzeyde bulunduğu, ayrıca UCP5'in testis dokusunda varlığı belirtilmiştir [17][18][19] Şekil 2.…”