Unknown

Dataset Information

0

Reactive Oxygen Species Generation by Reverse Electron Transfer at Mitochondrial Complex I Under Simulated Early Reperfusion Conditions.


ABSTRACT: Ischemic tissues accumulate succinate, which is rapidly oxidized upon reperfusion, driving a burst of mitochondrial reactive oxygen species (ROS) generation that triggers cell death. In isolated mitochondria with succinate as the sole metabolic substrate under non-phosphorylating conditions, 90% of ROS generation is from reverse electron transfer (RET) at the Q site of respiratory complex I (Cx-I). Together, these observations suggest Cx-I RET is the source of pathologic ROS in reperfusion injury. However, numerous factors present in early reperfusion may impact Cx-I RET, including: (i) High [NADH]; (ii) High [lactate]; (iii) Mildly acidic pH; (iv) Defined ATP/ADP ratios; (v) Presence of the nucleosides adenosine and inosine; and (vi) Defined free [Ca2+]. Herein, experiments with mouse cardiac mitochondria revealed that under simulated early reperfusion conditions including these factors, overall mitochondrial ROS generation was only 56% of that seen with succinate alone, and only 52% of this ROS was assignable to Cx-I RET. The residual non-RET ROS could be partially assigned to complex III (Cx-III) with the remainder likely originating from other ROS sources upstream of the Cx-I Q site. Together, these data suggest the relative contribution of Cx-I RET ROS to reperfusion injury may be overestimated, and other ROS sources may contribute a significant fraction of ROS in early reperfusion.

SUBMITTER: Fukushima CT 

PROVIDER: S-EPMC10690194 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Reactive Oxygen Species Generation by Reverse Electron Transfer at Mitochondrial Complex I Under Simulated Early Reperfusion Conditions.

Fukushima Caio Tabata CT   Dancil Ian-Shika IS   Clary Hannah H   Shah Nidhi N   Nadtochiy Sergiy M SM   Brookes Paul S PS  

bioRxiv : the preprint server for biology 20231121


Ischemic tissues accumulate succinate, which is rapidly oxidized upon reperfusion, driving a burst of mitochondrial reactive oxygen species (ROS) generation that triggers cell death. In isolated mitochondria with succinate as the sole metabolic substrate under non-phosphorylating conditions, 90% of ROS generation is from reverse electron transfer (RET) at the Q site of respiratory complex I (Cx-I). Together, these observations suggest Cx-I RET is the source of pathologic ROS in reperfusion injur  ...[more]

Similar Datasets

| S-EPMC10844975 | biostudies-literature
| S-EPMC2713566 | biostudies-literature
| S-EPMC9088781 | biostudies-literature
| S-EPMC9333399 | biostudies-literature
| S-EPMC3068929 | biostudies-literature
| S-EPMC10869518 | biostudies-literature
| S-EPMC9130584 | biostudies-literature
| S-EPMC4564374 | biostudies-literature
| S-EPMC10022631 | biostudies-literature
| S-EPMC8041852 | biostudies-literature