CFTR activity and mitochondrial function

Abstract

Abstract: Cystic Fibrosis(CF)isafrequentandlethalautosomalrecessivedisease,causedbymutationsinthe gene encodingtheCysticFibrosisTransmembraneConductanceRegulator(CFTR).Beforethediscovery of the CFTR gene, severalhypothesesattemptedtoexplaintheetiologyofthisdisease,includingthe possible roleofachloridechannel,diversealterationsinmitochondrialfunctions,theoverexpressionof the lysosomalenzyme a-glucosidaseandadeficiencyinthecytosolicenzymeglucose6-phosphate dehydrogenase.Becauseofthediversemitochondrialchangesfound,someauthorsproposedthatthe affectedgeneshouldcodifyforamitochondrialprotein.Later,theCFTRcloningandthedemonstration of itschloridechannelactivityturnedthemitochondrial,lysosomalandcytosolichypothesesobsolete. However,inrecentyears,usingnewapproaches,severalinvestigatorsreportedsimilarornew alterationsofmitochondrialfunctionsinCysticFibrosis,thusrediscoveringapossibleroleof mitochondriainthisdisease.Here,wereviewtheseCFTR-drivenmitochondrialdefects,including differentialgeneexpression,alterationsinoxidativephosphorylation,calciumhomeostasis,oxidative stress, apoptosisandinnateimmuneresponse,whichmightexplainsomecharacteristicsofthe complexCFphenotypeandrevealspotentialnewtargetsfortherapy.