Absence of mitochondrial uncoupling protein 1 affects apoptosis in thymocytes, thymocyte/T-cell profile and peripheral T-cell number

Abstract

Our laboratory has previously demonstrated the presence of constitutively expressed mitochondrial uncoupling protein 1 in mouse thymocytes. In our endeavours to understand the role of mitochondrial uncoupling protein 1 in thymocyte function, we compared cell profiles in thymus and spleen of wild-type with those of UCP 1 knock-out mice, which in turn led to comparative investigations of apoptotic potential in thymocytes from these mice. We demonstrate that spleen cell numbers were reduced approximately 3-fold in UCP 1 knock-out mice compared to wild-type mice. We record a halving of CD8 single positive cell numbers in thymus with a significant incremental increase in CD4/CD8 double positives cell numbers in the thymus of UCP 1 knock-out mice compared to wild-type mice. These data are mirrored by an approximate halving of CD8 single positive cell numbers and a doubling of CD4/CD8 double positive cell numbers in the spleen of UCP 1 knock-out mice compared to wild-type mice. These differences are most probably explained by our observations of decreased apoptotic potential and higher ATP levels in thymocytes of UCP 1 knock-out mice when compared to wild-type controls. We conclude that constitutively expressed UCP 1 is a factor in determining T-cell population selection in mice.

Mitochondrial electron transport chain, ROS generation and uncoupling (Review)

“…Interestingly, WAT can exert nonshivering thermogenesis with a UCP1-independent pathway (155,156). UCP1 has also been found in thymocytes and demonstrated to be involved in the maturation and fate determination of developing T-cells (157-159). Sale et al (160) found that UCP1 is expressed in islets and associates with the acute insulin response to glucose.…”

Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors:Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward

“…The reader can refer to excellent reviews on these subjects in ( 72 , 185 , 217 ). Also beyond the scope of this review are the role of constitutively expressed UCP1 in thymocytes as a factor in determining T cell population selection ( 4 , 76 ) and mitochondrial UCPs in plants ( 410 ) and unicellular eukaryotes ( 432 ).…”

A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats

“…In the current study, Ucp1 expression was increased in 12-mo-old recuperated thymi. Given that a murine thymic Ucp1 knockout model demonstrated decreased T-cell apoptosis (42), that increase may confer a potential for increased T-cell apoptosis in old recuperated rats.…”