Gliotoxin induces Mg2+ efflux from intact brain mitochondria.
Gliotoxin (GT) is a hydrophobic fungal metabolite of the epipolythiodioxopiperazine group which reacts with membrane thiols. When added to a suspension of energized brain mitochondria, it induces matrix swelling of low amplitude, collapse of membrane potential (DeltaPsi), and efflux of endogenous cations such as Ca2+ and Mg2+, typical events of mitochondrial permeability transition (MPT) induction. These effects are due to opening of the membrane transition pore. The addition of cyclosporin A (CsA) or ADP slightly reduces membrane potential collapse, matrix swelling and Ca2+ efflux; Mg2+ efflux is not affected at all. The presence of exogenous Mg2+ or spermine completely preserve mitochondria against DeltaPsi collapse, matrix swelling and Ca2+ release. Instead, Mg2+ efflux is only slightly affected by spermine. Our results demonstrate that, besides inducing MPT, gliotoxin activates a specific Mg2+ efflux system from brain mitochondria.
Salvi
Mauro
M
Dipartimento di Chimica Biologica, Universita' di Padova and Istituto di Neuroscienze del C.N.R., Unita' per lo Studio delle Biomembrane, Via G. Colombo 3, 35121 Padua, Italy.
Bozac
Aleksandra
A
Toninello
Antonio
A
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D005912:Gliotoxin / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D051381:Rats; D012015:Reference Standards
D007166:Immunosuppressive Agents; D000244:Adenosine Diphosphate; D005912:Gliotoxin; D016572:Cyclosporine; D008274:Magnesium; D002118:Calcium