| RRC ID |
76257
|
| 著者 |
Onukwufor JO, Farooqi MA, Vodičková A, Koren SA, Baldzizhar A, Berry BJ, Beutner G, Porter GA Jr, Belousov V, Grossfield A, Wojtovich AP.
|
| タイトル |
A reversible mitochondrial complex I thiol switch mediates hypoxic avoidance behavior in C. elegans.
|
| ジャーナル |
Nat Commun
|
| Abstract |
C. elegans react to metabolic distress caused by mismatches in oxygen and energy status via distinct behavioral responses. At the molecular level, these responses are coordinated by under-characterized, redox-sensitive processes, thought to initiate in mitochondria. Complex I of the electron transport chain is a major site of reactive oxygen species (ROS) production and is canonically associated with oxidative damage following hypoxic exposure. Here, we use a combination of optogenetics and CRISPR/Cas9-mediated genome editing to exert spatiotemporal control over ROS production. We demonstrate a photo-locomotory remodeling of avoidance behavior by local ROS production due to the reversible oxidation of a single thiol on the complex I subunit NDUF-2.1. Reversible thiol oxidation at this site is necessary and sufficient for the behavioral response to hypoxia, does not respond to ROS produced at more distal sites, and protects against lethal hypoxic exposure. Molecular modeling suggests that oxidation at this thiol residue alters the ability for NDUF-2.1 to coordinate electron transfer to coenzyme Q by destabilizing the Q-binding pocket, causing decreased complex I activity. Overall, site-specific ROS production regulates behavioral responses and these findings provide a mechanistic target to suppress the detrimental effects of hypoxia.
|
| 巻・号 |
13(1)
|
| ページ |
2403
|
| 公開日 |
2022-5-3
|
| DOI |
10.1038/s41467-022-30169-y
|
| PII |
10.1038/s41467-022-30169-y
|
| PMID |
35504873
|
| PMC |
PMC9064984
|
| MeSH |
Animals
Avoidance Learning
Caenorhabditis elegans* / genetics
Caenorhabditis elegans* / metabolism
Electron Transport Complex I / genetics
Electron Transport Complex I / metabolism
Hypoxia
Reactive Oxygen Species / metabolism
Sulfhydryl Compounds*
|
| リソース情報 |
| 線虫 |
tm760 |
