title: Many faces of mitochondrial uncoupling during age: damage or defense?
abstract: An increased mitochondrial proton leak occurs in aging, but the origin of such modification remains unclear. This study defined the cause of mitochondrial uncoupling in mitotic (liver) and postmitotic (heart) rat tissues during aging and its effects on energy homeostasis and free radical production. Proton leak in old heart mitochondria was dependent on uncoupling proteins' upregulation, whereas it was caused by alterations in the mitochondrial membrane composition in old liver. ATP homeostasis was impaired in both tissues from old animals and was associated to disrupted F0F1-ATPase activity. H2O2 production rate and 4-hydroxy-2-nonenalprotein adducts were higher in old liver mitochondria compared with young liver mitochondria, but they were similar in heart mitochondria from both groups. Moreover, key mitochondrial biogenesis regulators were upregulated in old liver but downregulated in old heart. In conclusion, uncoupling proteins mediate proton leak and avoid oxidative damage in heart, acting as a protective mechanism. This does not occur in liver, where ATP depletion and oxidative stress may stimulate mitochondrial biogenesis and eliminate damaged cells.
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università di Foggia 71122, Foggia, Italy. g.vendemiale@unifg.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellanti
authors.forename: Antonino Davide
authors.initials: AD
authors.lastname: Romano
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Giudetti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rollo
authors.forename: Maria
authors.initials: M
authors.lastname: Blonda
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tamborra
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Vendemiale
authors.forename: Gaetano
authors.initials: G
authors.lastname: Serviddio
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics / Q000378:metabolism; D033742:Adenine Nucleotide Translocator 2 / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006019:Glycolysis; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008929:Mitochondria, Heart / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D011522:Protons; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D033741:Adenine Nucleotide Translocator 1; D033742:Adenine Nucleotide Translocator 2; D005227:Fatty Acids; D005609:Free Radicals; D007473:Ion Channels; D024101:Mitochondrial Proteins; D011522:Protons; D012333:RNA, Messenger; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D000255:Adenosine Triphosphate
keywords: Mitochondrial biogenesis.; Mitochondrial proton leak; Oxidative stress; Uncoupling proteins