A Study of Mitochondrial Function in An Essential Hypertension Family Carrying Mitochondrial tRNA^Met4435A>G Mutation

In this study, we explore the effects of tRNAMet4435A>G mutation on the mitochondrial function in patients with essential hypertention. First, lymphocytes extracted from venous blood of an essential hypertention family carrying tRNAMet4435A>G mutation were translated into immortalized lymphocytes, and established as the mutant group. Meanwhile, normal immortalized lymphocytes with the same G2a1 haplotype were selected as the control group. Second, the steady-state level analysis of tRNAs, aminoacylation analysis of tRNAs, Western blot analysis, mitochondrial ATP level detection and the level of membrane potential were performed to reflect the functional of mitochondria. We investigated that cell lines carrying the tRNAMet4435A>G mutation exhibited significantly decreased steady-state level of tRNAMet (P<0.05) and aminoacylation of tRNAMet (P=0.023) as compared with control group. The aberrant tRNAMet metabolism resulted in decrease of mitochondrial polypeptides in the mutant group. And according to the results of Western blot, the level of CO2, ATP6 and ND3 in mutant group decreased 11.80%, 42.70% and 46.08% respectively when compared with control group. Furthermore, the m.4435A>G mutation caused respiratory deficiency, markedly diminished mitochondrial ATP levels and membrane potential. And combined with these two experiments, cell lines with tRNAMet4435A>G mutation did decrease 28.50% (P<0.001) mitochondrial ATP level and drop 38.50% (P<0.001) level of membrane potential. Thus, tRNAMet4435A>G mutation caused the decrease of steady-state level of tRNAMet, aminoacylation of tRNAMet, mitochondrial translation defect, mitochondrial ATP level and membrane potential. These showed tRNAMet4435A>G mutation affected the structure and function of tRNA, thus changing the function of mitochondria.

CSTR: 32200.14.cjcb.2020.02.0007