Mitochondrial oxidative phosphorylation and dynamics in mouse liver infected with Plasmodium berghei and the modulatory effects of a novel compound purified from Phyllanthus amarus

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Abstract Mitochondria occupy prominent position in cell metabolism, however, infection of the host by Plasmodium species causes their dysfunction and imbalance in homeostasis. Antimalarial orthodox drugs affect oxidative phosphorylation and mitochondrial dynamics in the host cell. In this study, we observed the influence of 1, 3, 16 trimethoxy-10 methyl-17-(pent-3-enyl)cyclopenta[α]phenanthrene (TMCP) purified from Phyllanthus amarus on oxidative phosphorylation and mitochondrial dynamics in Plasmodium berghei-infected mice by assessing the extent of mRNA of mitochondrial complexes and proteins responsible for mitochondrial biogenesis, fission and fusion. P. berghei decreases the expressions of complexes I to V while TMCPT at both doses (5 and 10 mg/kg) increased them. The PGC-1α, prohibitins 1 and 2 that P. berghei infection decreased in the infected control was increased significantly by TMCP (5 mg/kg). Increase in DRP-1 mediates mitochondrial fission in the infected mice treated with TMCP while significant expressions of OPA1 and mitofusin1 in mice treated with TMCP (5 mg/kg) elicit significant mitochondrial fusion. The TMCP (5 mg/kg) initiated PINK 1-dependent mitophagy while maximum FUNDC1 expression signified full modulation of hypoxia-induced autophagy. Furthermore, TMCP initiated up-regulation of prohibitins 1 and 2 relative to the infected control. The results obtained in this study indicates that TMCP prevents bioenergetic stress and modulate mitochondrial dynamics for effective mitophagy.

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