Science (New York, N.Y.) · 2025
Running a genetic stop sign accelerates oxygen metabolism and energy production in horses.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Castiglione Gianni M, Chen Xin, Xu Zhenhua, Dbouk Nadir H, Bose Anamika A, Carmona-Berrio David, Chi Emiliana E, Zhou Lingli, Boronina Tatiana N, Cole Robert N, Wu Shirley, Liu Abby D, Liu Thalia D, Lu Haining, Kalbfleisch Ted, Rinker David, Rokas Antonis, Ortved Kyla, Duh Elia J
Аннотация
Horses are among nature's greatest athletes, yet the ancestral molecular adaptations fueling their energy demands are poorly understood. Within a clinically important pathway regulating redox and metabolic homeostasis (NRF2/KEAP1), we discovered an ancient mutation-conserved in all extant equids-that increases mitochondrial respiration while decreasing tissue-damaging oxidative stress. This mutation is a de novo premature opal stop codon in KEAP1 that is translationally recoded into a cysteine through previously unknown mechanisms, producing an R15C mutation in KEAP1 that is more sensitive to electrophiles and reactive oxygen species. This recoding enables increased NRF2 activity, which enhances mitochondrial adenosine 5'-triphosphate production and cellular resistance to oxidative damage. Our study illustrates how recoding of a de novo stop codon, a strategy thought restricted to viruses, can facilitate adaptation in vertebrates.