Lyn-mediated mitochondrial tyrosine phosphorylation is required to preserve mitochondrial integrity in early liver regeneration.
Functional alterations in mitochondria such as overproduction of ROS (reactive oxygen species) and overloading of calcium, with subsequent change in the membrane potential, are traditionally regarded as pro-apoptotic conditions. Although such events occur in the early phases of LR (liver regeneration) after two-thirds PH (partial hepatectomy), hepatocytes do not undergo apoptosis but continue to proliferate until the mass of the liver is restored. The aim of the present study was to establish whether tyrosine phosphorylation, an emerging mechanism of regulation of mitochondrial function, participates in the response to liver injury following PH and is involved in contrasting mitochondrial pro-apoptotic signalling. Mitochondrial tyrosine phosphorylation, negligible in the quiescent liver, was detected in the early phases of LR with a trend similar to the events heralding mitochondrial apoptosis and was attributed to the tyrosine kinase Lyn, a member of the Src family. Lyn was shown to accumulate in an active form in the mitochondrial intermembrane space, where it was found to be associated with a multiprotein complex. Our results highlight a role for tyrosine phosphorylation in accompanying, and ultimately counteracting, mitochondrial events otherwise leading to apoptosis, hence conveying information required to preserve the mitochondrial integrity during LR.
Gringeri
Enrico
E
Department of General Surgery, Hepatobiliary and Liver Transplant Unit, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
Carraro
Amedeo
A
Tibaldi
Elena
E
D'Amico
Francesco E
FE
Mancon
Mario
M
Toninello
Antonio
A
Pagano
Mario A
MA
Vio
Claudia
C
Cillo
Umberto
U
Brunati
Anna M
AM
D000818:Animals; D017209:Apoptosis; D006498:Hepatectomy; D008115:Liver Regeneration / Q000502:physiology*; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D014443:Tyrosine; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases