Reactive Oxygen Species Special Feature: Oxygen-regulated isoforms of cytochrome c oxidase have differential effects on its nitric oxide production and on hypoxic signaling

@article{citeulike:2904721, abstract = {Recently, it has been reported that mitochondria possess a novel pathway for nitric oxide (NO) synthesis. This pathway is induced when cells experience hypoxia, is nitrite (NO2-)-dependent, is independent of NO synthases, and is catalyzed by cytochrome c oxidase (Cco). It has been proposed that this mitochondrially produced NO is a component of hypoxic signaling and the induction of nuclear hypoxic genes. In this study, we examine the NO2--dependent NO production in yeast engineered to contain alternative isoforms, Va or Vb, of Cco subunit V. Previous studies have shown that these isoforms have differential effects on oxygen reduction by Cco, and that their genes (COX5a and COX5b, respectively) are inversely regulated by oxygen. Here, we find that the Vb isozyme has a higher turnover rate for NO production than the Va isozyme and that the Vb isozyme produces NO at much higher oxygen concentrations than the Va isozyme. We have also found that the hypoxic genes CYC7 and OLE1 are induced to higher levels in a strain carrying the Vb isozyme than in a strain carrying the Va isozyme. Together, these results demonstrate that the subunit V isoforms have differential effects on NO2--dependent NO production by Cco and provide further support for a role of Cco in hypoxic signaling. These findings also suggest a positive feedback mechanism in which mitochondrially produced NO induces expression of COX5b, whose protein product then functions to enhance the ability of Cco to produce NO in hypoxic/anoxic cells. 10.1073/pnas.0709461105}, author = {Castello, Pablo R. and Woo, Dong K. and Ball, Kerri and Wojcik, Jay and Liu, Laura and Poyton, Robert O. }, citeulike-article-id = {2904721}, comment = {reports on the production of NO from nitrite by mitochondrial cyt c oxidase}, doi = {http://dx.doi.org/10.1073/pnas.0709461105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {anaerobic, biochemistry, cytc, cytochrome, denitrification, nitric}, month = {June}, number = {24}, pages = {8203--8208}, posted-at = {2008-06-18 10:01:34}, priority = {2}, title = {Reactive Oxygen Species Special Feature: Oxygen-regulated isoforms of cytochrome c oxidase have differential effects on its nitric oxide production and on hypoxic signaling}, url = {http://dx.doi.org/10.1073/pnas.0709461105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:2904721 L3 - citeulike-article-id:2904721 TI - Reactive Oxygen Species Special Feature: Oxygen-regulated isoforms of cytochrome c oxidase have differential effects on its nitric oxide production and on hypoxic signaling JF - Proceedings of the National Academy of Sciences VL - 105 IS - 24 SP - 8203 EP - 8208 N2 - Recently, it has been reported that mitochondria possess a novel pathway for nitric oxide (NO) synthesis. This pathway is induced when cells experience hypoxia, is nitrite (NO2-)-dependent, is independent of NO synthases, and is catalyzed by cytochrome c oxidase (Cco). It has been proposed that this mitochondrially produced NO is a component of hypoxic signaling and the induction of nuclear hypoxic genes. In this study, we examine the NO2--dependent NO production in yeast engineered to contain alternative isoforms, Va or Vb, of Cco subunit V. Previous studies have shown that these isoforms have differential effects on oxygen reduction by Cco, and that their genes (COX5a and COX5b, respectively) are inversely regulated by oxygen. Here, we find that the Vb isozyme has a higher turnover rate for NO production than the Va isozyme and that the Vb isozyme produces NO at much higher oxygen concentrations than the Va isozyme. We have also found that the hypoxic genes CYC7 and OLE1 are induced to higher levels in a strain carrying the Vb isozyme than in a strain carrying the Va isozyme. Together, these results demonstrate that the subunit V isoforms have differential effects on NO2--dependent NO production by Cco and provide further support for a role of Cco in hypoxic signaling. These findings also suggest a positive feedback mechanism in which mitochondrially produced NO induces expression of COX5b, whose protein product then functions to enhance the ability of Cco to produce NO in hypoxic/anoxic cells. 10.1073/pnas.0709461105 KW - anaerobic KW - biochemistry KW - cytc KW - cytochrome KW - denitrification KW - nitric N1 - reports on the production of NO from nitrite by mitochondrial cyt c oxidase AU - Castello, Pablo AU - Woo, Dong AU - Ball, Kerri AU - Wojcik, Jay AU - Liu, Laura AU - Poyton, Robert PY - 2008/06/17/ UR - http://dx.doi.org/10.1073/pnas.0709461105 ER -