Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1

Abstract

Thioredoxins (TRX) are traditionally considered as enzymes catalyzing redox reactions. However, redox-independent functions of thioredoxins have been described in different organisms, although the underlying molecular mechanisms are yet unknown. We report here the characterization of the first generated endogenous redox-inactive thioredoxin in an animal model, the TRX-1 in the nematode Caenorhabditis elegans . We find that TRX-1 dually regulates the formation of an endurance larval stage (dauer) by interacting with the insulin pathway in a redox-independent manner and the cGMP pathway in a redox-dependent manner. Moreover, the requirement of TRX-1 for the extended longevity of worms with compromised insulin signalling or under calorie restriction relies on TRX-1 redox activity. In contrast, the nuclear translocation of the SKN-1 transcription factor and increased LIPS-6 protein levels in the intestine upon trx-1 deficiency are strictly redox-independent. Finally, we identify a novel function of C. elegans TRX-1 in male food-leaving behaviour that is redox-dependent. Taken together, our results position C. elegans as an ideal model to gain mechanistic insight into the redox-independent functions of metazoan thioredoxins, overcoming the limitations imposed by the embryonic lethal phenotypes of thioredoxin mutants in higher organisms.

Pediococcus acidilactici Promotes the Longevity of C. elegans by Regulating the Insulin/IGF-1 and JNK/MAPK Signaling, Fat Accumulation and Chloride Ion

“…To measure the lifespan of C. elegans accurately, agesynchronized worms of the wild-type strain (N2) were grown on NGM agar plates containing live E. coli OP50 at 20 • C, until they reached the young adult stage. Approximately 80-100 age-synchronized worms were then transferred to fresh NGM plates covered with lawns of E. coli OP50 or PA (21). The plates were incubated at 20 • C, the worms were transferred every other day thereafter.…”

Mitochondrial thioredoxin system is required for enhanced stress resistance and extended longevity in long-lived mitochondrial mutants

“…These results suggest that thioredoxins and or thioredoxin reductases have additional roles that are independent of the other. One possible explanation for these differences is the fact that thioredoxins have redox-independent functions [ [23] , [24] , [25] , [26] , [27] ]. Disruption of the thioredoxin gene would affect both redox-dependent and redox-independent functions, while disruption of the thioredoxin reductase genes would be predicted to only affect the redox-dependent functions of its corresponding thioredoxin.…”

“…Interestingly, thioredoxins have also been shown to have redox-independent functions. For example, modifying TRX-1 to disrupt its redox activity does not prevent TRX-1 from acting as a chaperone protein [ 23 , 24 ], promoting degradation of the apoptosis-regulating kinase ASK1 [ 25 ], facilitating dauer formation in daf-28 mutants [ 26 ], mediating avoidance of bacterial pathogens [ 27 ], or allowing for the nuclear localization of the oxidative-stress responsive transcription factor SKN-1 and subsequent upregulation of its target gene lips-6 [ 26 ].…”

Distinct mechanisms underlie H2O2 sensing in C. elegans head and tail

“…At high H 2 O 2 concentrations, Prxs become hyperoxidized, a form that has been shown to function as a molecular chaperone [ 19 , 20 ]. Similarly, thioredoxins have been shown to have redox-independent function [ 21 , 22 ]. As pivotal antioxidants, Prxs dysfunction has been associated with several pathologies [ 23 ], including cancer [ 24 ].…”