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Sazonova et al. Threshold heteroplasmy levels of atherogenic mutations

some ribosomes in mitochondria and to a decrease in the synthesis of cytochrome B, which becomes 244
synthesis of respiratory chain enzymes. amino acids shorter. Perhaps, this mutation leads to
the dysfunction of complex III of the respiratory chain.
Single nucleotide substitution m.3336T>C (MT-ND1 As a result of this process, atherosclerotic lesions can
gene) is a silent mutation. In case of its occurrence, develop in the cells and arteries in general.
there is no replacement of the amino acid in the first
protein subunit of NADH dehydrogenase. Meanwhile, It is necessary to note the novelty and uniqueness of
the mutation is associated with atherosclerotic lesions. this study. According to the analysis of literary sources,
Probably, this mutation is linked to an atherogenic there is not any scientific article in the world where the
haplotype. threshold heteroplasmy level of mitochondrial genome
mutations and their association with predisposition to
Mutation m.5178C>A (MT-ND2 gene) results in the atherosclerosis has been studied. In addition, there
replacement of an amino acid (Leu>Met). Although are not any similar works for other human diseases
in some earlier literary sources [45] it is reported that either.
m.5178C>A is anti-atherogenic, in this study, in a
sample of 700 study participants, the association of Information about the threshold heteroplasmy level
this mutation with atherosclerotic lesions was found. in mitochondrial genome mutations, associated
Probably in earlier studies, an undersampling has with atherosclerosis and its risk factors, can help in
played a role. assessing the predisposition and the early diagnostics
of these pathologies. The obtained data can be used
The single nucleotide replacement of guanine by to create test systems for atherosclerosis diagnostics.
adenine at the position of the mitochondrial genome
12315 results in a change in the tertiary structure of In conclusion, the article dedicated to detection of a
the transport RNA-Leu (recognition codon CUN). threshold heteroplasmy level of mitochondrial genome
It can lead to a dysfunction of this tRNA, leading mutations in patients with atherosclerotic lesions in
to a decrease in synthesis of the protein chains in blood vessels, is quite relevant and well-timed. This
respiratory chain enzymes, which contain amino acid work is characterized by a high degree of novelty,
leucine. because similar works in world literature are absent.
Using the method, developed in our laboratory [16,17] ,
Mutation m.13513G>A leads to the replacement of we managed to determine threshold heteroplasmy
the amino acid (Asp>Asn) in the 5th protein subunit of levels of 11 mitochondrial genome mutations
the respiratory chain enzyme NADH-dehydrogenase. associated with atherosclerosis. We suppose that
Perhaps, as a result of this mutation, the efficiency threshold heteroplasmy levels of these mutations is
of complex 1 of the respiratory chain, leading to an a new criterion for evaluation of predisposition to the
increase in the production of energy in the cell, is occurrence and development of atherosclerotic lesions
improved. Our research team discovered the anti- in human arteries.
atherogenic effect of this mutation.

Mutation m.14459G>A (MT-ND6 gene) results in DECLARATIONS
amino acid substitution (Ala>Val) at position 72 of the
6th protein subunit of NADH dehydrogenase. Probably, Authors’ contributions
this mutation causes a defect in the enzyme, leading to Study design: M.A. Sazonova
the appearance of atherosclerotic lesions. Data collection: M.A. Sazonova, E.V. Galitsyna, V.A.
Orekhova
The single nucleotide substitution m.14846G>A (MT- Experimental studies: M.A. Sazonova, A.I. Ryzhkova,
CYTB gene) results in the amino acid substitution V.V. Sinyov
(Gly>Ser) of cytochrome B. Probably, this mutation Literature search: A.A. Melnichenko
stabilizes the complex of the III respiratory chain, into Statistical analysis: I.A. Sobenin
which this cytochrome is included. The result of this Manuscript writing, preparation and editing: M.A.
mutation may be an increase in the synthesis of ATP Sazonova
in the cell. It can protect cells and tissues from the Manuscript review: A.N. Orekhov, A.L. Ravani
occurrence of atherosclerosis.
Financial support and sponsorship
Mutation m.15059G>A, localized in the MT-CYTB This work was supported by the Russian Scientific
gene, leads to a formation of a stop codon. This stops Foundation (Grant #14-14-01038).

Vessel Plus ¦ Volume 1 ¦ December 28, 2017 189