Forskningsoutput per år
Forskningsoutput per år
Johannes K. Ehinger, Sarah Piel, Rhonan Ford, Michael Karlsson, Fredrik Sjövall, Eleonor Åsander Frostner, Saori Morota, Robert W. Taylor, Doug M. Turnbull, Clive Cornell, Steven J. Moss, Carsten Metzsch, Magnus J. Hansson, Hans Fliri, Eskil Elmér
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review
Mitochondrial complex I (CI) deficiency is the most prevalent defect in the respiratory chain in paediatric mitochondrial disease. This heterogeneous group of diseases includes serious or fatal neurological presentations such as Leigh syndrome and there are very limited evidence-based treatment options available. Here we describe that cell membrane-permeable prodrugs of the complex II substrate succinate increase ATP-linked mitochondrial respiration in CI-deficient human blood cells, fibroblasts and heart fibres. Lactate accumulation in platelets due to rotenone-induced CI inhibition is reversed and rotenone-induced increase in lactate:pyruvate ratio in white blood cells is alleviated. Metabolomic analyses demonstrate delivery and metabolism of [ 13 C]succinate. In Leigh syndrome patient fibroblasts, with a recessive NDUFS2 mutation, respiration and spare respiratory capacity are increased by prodrug administration. We conclude that prodrug-delivered succinate bypasses CI and supports electron transport, membrane potential and ATP production. This strategy offers a potential future therapy for metabolic decompensation due to mitochondrial CI dysfunction.
Originalspråk | engelska |
---|---|
Artikelnummer | 12317 |
Tidskrift | Nature Communications |
Volym | 7 |
DOI | |
Status | Published - 2016 aug. 9 |
Forskningsoutput: Tidskriftsbidrag › Översiktsartikel › Peer review
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)
Elmer, E. (PI), Ehinger, J. (CoI), Chamkha, I. (Forskare), Åsander Frostner, E. (Forskningsingenjör) & Sjövall, F. (Forskare)
2019/07/01 → …
Projekt: Forskning
Elmer, E. (PI), Ehinger, J. (CoPI), Hansson, M. (Forskare), Åsander Frostner, E. (Forskarstuderande), Chamkha, I. (Forskare), Karlsson, M. (Forskarstuderande), Marelsson, S. (Forskarstuderande), Sjövall, F. (Forskare) & Westerlund, E. (Forskare)
2013/04/01 → …
Projekt: Forskning
Elmer, E. (PI), Hansson, M. (Forskare), Piel, S. (Forskare), Ehinger, J. (Forskare), Karlsson, M. (Forskare), Chamkha, I. (Forskare), Westerlund, E. (Forskare), Åsander Frostner, E. (Forskningsingenjör), Sjövall, F. (Forskare) & Marelsson, S. (Forskarstuderande)
Crafoordska stiftelsen, Linnéa och Josef Carlssons stiftelse
2012/05/01 → …
Projekt: Forskning
Åsander Frostner, E. (Roll ej angiven)
Aktivitet: Deltagit i eller arrangerat evenemang › Deltagit i konferens
Åsander Frostner, E. (deltagare)
Aktivitet: Deltagit i eller arrangerat evenemang › Deltagit i konferens
Piel, S. (deltagare)
Aktivitet: Deltagit i eller arrangerat evenemang › Deltagit i konferens