Biological Significance of Enhanced Mitochondrial Membrane Potential in Regenerating Liver

Abstract

Liver mitochondrial membrane potential was assessed during regeneration following partial hepatectomy in rabbits. Absorbance change of safranine O per milligram of mitochondrial protein was used to evaluate mitochondrial membrane potential. Absorbance change was calibrated to the membrane potential in millivolts produced by valinomycin-induced potassium diffusion potential. At 24 hr after hepatectomy, absorbance change of safranine O per milligram of mitochondrial protein increased from 15.0 +/- 2.2 X 10(-3) to 37.4 +/- 3.3 X 10(-3) per mg (p less than 0.005). This represents a mitochondrial membrane potential increase from 77.0 +/- 4.6 to 124.4 +/- 6.7 mV. Phosphorylative activity increased from 59.9 +/- 5.0 to 106.1 +/- 7.4 nmoles ATP synthesized per mg per min (p less than 0.005). The enhancement of phosphorylative activity was closely linked to the elevation in liver mitochondrial membrane potential (r = 0.77, p less than 0.005). We suggest that elevation of mitochondrial membrane potential, coupled with enhanced oxidative and phosphorylative activities, plays an important role in the regeneration process following hepatectomy.

Changes in Mitochondrial Adenine Nucleotides and in Permeability Transition in Two Models of Rat Liver Regeneration

“…In addition, increase of ⌬ (30 mV; negative inside), correlates with oxidative and phosphorylative activities. 3 However, it has been suggested also that decreased amount of ␤-subunit of F 1 component of mitochondrial adenosine triphosphatase induces a brief period of low ⌬H ϩ during the PH-induced LR. 4 This enhanced passive proton conductivity can cause a collapse of respiratory ⌬H ϩ , leading to low respiratory control and uncoupled oxidative phosphorylation 27 and would correlate with low mitochondrial GSH concentration, increased oxygen radicals and malondialdehyde production, and altered mitochondria function at the early prereplicative phase of LR.…”

“…Here, mitochondrial activated respiration (state 3) and generation of adenosine triphosphate (ATP), markedly exceed the corresponding activities in control animals. 1,2 During PH-induced rat liver regeneration (LR), mitochondria show enhanced mitochondrial membrane potential (⌬) and phosphorylative capacity, in the remaining hepatocytes, 3 despite that a lack of enhanced gene expression of mitochondrial proteins (i.e., cytochrome oxidase subunits) also has been found at early times after PH. 4 Enhanced mitochondrial oxygen consumption could increase reactive oxygen species generation, leading to lower mitochondrial oxidative phosphorylation during the early prereplicative phase of PH-induced LR.…”

Platelet Activating Factor (PAF) Antagonism with Ginkgolide B Protects the Liver Against Acute Injury. Importance of Controlling the Receptor of PAF

“…Additionally, the histologic analysis of BN52021-treated tissue showed that the grade of both necrotic and apoptotic process was decreased and attenuated by the administration of PAF-R antagonist. The ability of the liver to maintain functional and structural integrity against the injury resulting from APAP intoxication is dependent on the energy supply from oxidative and phosphorylative activities of mitochondria [54,55]. In the BN52021-treated group, the rapid recovery of energy charge of the liver, which is a balance between energy generating and consuming reactions [56], along with a lower concentration of AST, was indicative of prompt restoration of the mitochondrial function from these injuries.…”

Recombinant Platelet-Activating Factor–Acetylhydrolase Attenuates Paracetamol-Induced Liver Oxidative Stress, Injury, and Regeneration

“…Additionally, the histologic analysis of rPAF-AH-treated tissue showed that the grade of both the necrotic and the apoptotic process was decreased and attenuated by the administration of PAF inactivator. The ability of the liver to maintain functional and structural integrity against the injury resulting from APAP intoxication is dependent on the energy supply from oxidative and phosphorylative activities of mitochondria [54,55]. In the rPAF-AHtreated group, the rapid recovery of the energy charge of the liver, which is a balance between energy generating and energy consuming reactions [56], along with the lower concentration of AST, was indicative of prompt restoration of the mitochondrial function from these injuries.…”