Formation of dinitrosyl iron complexes in cardiac mitochondria

Differential mitochondrial dinitrosyliron complex formation by nitrite and nitric oxide

“…Given the essential role of the mitochondrion in the mechanism of nitrite-mediated protection after I/R and the prior evidence of in vitro mitochondrial DNIC formation during anoxia [18] , [22] , we examined whether dietary nitrite supplementation resulted in mitochondrial DNIC formation. Fractionation of liver tissue from nitrite supplemented (3 g/L) mice showed that significant DNIC was formed in the mitochondrial compartment ( Fig.…”

“…Mitochondrial aconitase is an iron-sulfur protein that is a major target for oxidation, resulting in the loss of its activity. Additionally, its iron centers have previously been identified as a potential target for DNIC formation [20] , [22] . Measurement of aconitase activity in the isolated mitochondria subjected to anoxia/reoxygenation showed that aconitase activity was significantly decreased after anoxia/reoxygenation ( Fig.…”

“…However, our data demonstrating nitrite-dependent DNIC formation in isolated mitochondria are consistent with de novo DNIC formation within the organelle rather than import. While the exact proportion of tissue DNIC that accumulates within the mitochondrion is unclear, it is well established that the organelle contains a pool of free iron that potentially contributes to DNIC formation [18] , [22] . Further, nitrite has been shown to enter the mitochondrion, where it can be reduced to NO by a number of proteins including cytochrome c or cytochrome c oxidase [47] , [48] .…”

“…In contrast, other reports have associated DNIC formation with cytotoxicity and pathogenesis. Mechanistically, cytotoxicity has been attributed to the disruption of iron containing enzymes, such as the iron-sulfur protein aconitase [16] , [20] , [22] , [36] . Our data could be consistent with both a protective and toxic effect of DNIC.…”

“…While nitrite is known to form DNIC, the formation of this species by nitrite versus NO has not been compared [18] , [19] , [20] . Further, DNIC have been reported to have both cytoprotective and cytotoxic roles physiologically, but it remains unclear whether DNIC formation contributes to biological effects mediated by nitrite [16] , [18] , [21] , [22] , [23] , [24] .…”