Function and expression study uncovered hepatocyte plasma membrane ecto-ATP synthase as a novel player in liver regeneration.
ATP synthase, canonically mitochondrially located, is reported to be ectopically expressed on the plasma membrane outer face of several cell types. We analysed, for the first time, the expression and catalytic activities of the ecto- and mitochondrial ATP synthase during liver regeneration. Liver regeneration was induced in rats by two-thirds partial hepatectomy. The protein level and the ATP synthase and/or hydrolase activities of the hepatocyte ecto- and mitochondrial ATP synthase were analysed on freshly isolated hepatocytes and mitochondria from control, sham-operated and partial hepatectomized rats. During the priming phase of liver regeneration, 3 h after partial hepatectomy, liver mitochondria showed a marked lowering of the ATP synthase protein level that was reflected in the impairment of both ATP synthesis and hydrolysis. The ecto-ATP synthase level, in 3 h partial hepatectomized hepatocytes, was decreased similarly to the level of the mitochondrial ATP synthase, associated with a lowering of the ecto-ATP hydrolase activity coupled to proton influx. Noteworthily, the ecto-ATP synthase activity coupled to proton efflux was completely inhibited in 3 h partial hepatectomized hepatocytes, even in the presence of a marked intracellular acidification that would sustain it as in control and sham-operated hepatocytes. At the end of the liver regeneration, 7 days after partial hepatectomy, the level and the catalytic activities of the ecto- and mitochondrial ATP synthase reached the control and sham-operated values. The specific modulation of hepatocyte ecto-ATP synthase catalytic activities during liver regeneration priming phase may modulate the extracellular ADP/ATP levels and/or proton influx/efflux trafficking, making hepatocyte ecto-ATP synthase a candidate for a novel player in the liver regeneration process.
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70100, Italy.
Federica
F
Taurino
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70100, Italy.
Caterina
C
Giannoccaro
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70100, Italy Center of Integrated Research, Campus Bio-Medico, University of Rome, Rome 00100, Italy.
Anna Maria
AM
Sardanelli
Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce 73100, Italy.
Alessandro
A
Cavallo
Center for Biomolecular Nanotechnologies (CBN), Istituto Italiano di Tecnologia Via Barsanti 14, 73010 Arnesano (Lecce), Italy.
Elisa
E
De Luca
Department of Emergency and Organ Transplants, University of Bari "Aldo Moro", Bari 70100, Italy.
Salvatore
S
Santacroce
Institute of Biomembranes and Bioenergetics, National Research Council, Bari 70100, Italy.
Sergio
S
Papa
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70100, Italy.
Franco
F
Zanotti
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70100, Italy Center of Integrated Research, Campus Bio-Medico, University of Rome, Rome 00100, Italy antonio.gnoni@uniba.it.
Antonio
A
Gnoni
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D055162:Biocatalysis; D006498:Hepatectomy; D008115:Liver Regeneration; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D008565:Membrane Proteins; D000251:Adenosine Triphosphatases; C474451:F1F0-ATP synthase; C027201:ectoATPase; D025261:Mitochondrial Proton-Translocating ATPases
ATP synthase; ecto-ATP synthase; extracellular ATP/ADP; hepatocytes; liver regeneration; proton trafficking