Potential Roles of mtDNA Mutations in PCOS-IR: A Review

Figures & data

Figure 1 Influence of hyperinsulinemia on various human organs.

Figure 2 Summarized scheme of the pathophysiology of PCOS.

Abbreviations: GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; FSH, follicule-stimulating hormone; SHBG, sex hormone –binding globulin.

Figure 3 Genetic map of human mitochondrial genome, which has a 16,569 bp sequence. Red boxes indicated PCOS-IR–associated mtDNA mutations.

Figure 4 Heteroplasmy and the threshold effect.

Figure 5 (A-G) Cloverleaf structure of mt-tRNA genes, arrows indicate the positions of PCOS-IR related mutations.

Table 1 Summary of PCOS-IR–associated Mt-tRNA mutations

tRNA species	Allele	Nucleotide position in tRNAs	Structure location	Homoplasmy/heteroplasmy	Aberrant tRNA Biology	References
tRNA^Leu(UUR)	C3275T	44	Variable region	Homoplasmy	Disrupts conserved base-pairing	[69]
	A3302G	71	Acceptor arm	Heteroplasmy	Affects 3’-end processing	[65]
tRNA^Gln	T4363C	38	Anticodon stem	Homoplasmy	Affects tRNA posttranscriptional modification	[69]
	T4395C	6	Acceptor arm	Homoplasmy	Creates new base-pairing	[69]
tRNA^Cys	G5821A	6	Acceptor arm	Homoplasmy	Disrupts conserved base-pairing	[75,76]
tRNA^Ser(UCN)	C7492T	26	Anticodon stem	Homoplasmy	Creates new base-pairing	[52]
tRNA^Asp	A7543G	29	Anticodon stem	Heteroplasmy	Affects tRNA aminoacylation and steady-state level	[71]
tRNA^Lys	A8343G	54	TψC loop	Homoplasmy	Affects tRNA posttranscriptional modification	[69]
tRNA^Glu	A14693G	54	TψC loop	Homoplasmy	Affects tRNA posttranscriptional modification	[46,71]

Ding Y, Xia BH, Zhang CJ, et al. Mitochondrial tRNALeu(UUR) C3275T, tRNAGln T4363C and tRNALys A8343G mutations may be associated with PCOS and metabolic syndrome. Gene. 2018;642:299–306. doi:10.1016/j.gene.2017.11.049

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Ding Y, Zhuo G, Zhang C, et al. Point mutation in mitochondrial tRNA gene is associated with polycystic ovary syndrome and insulin resistance. Mol Med Rep. 2016;13(4):3169–3172. doi:10.3892/mmr.2016.4916

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Ding Y, Xia BH, Zhang CJ, et al. Mutations in mitochondrial tRNA genes may be related to insulin resistance in women with polycystic ovary syndrome. Am J Transl Res. 2017;9(6):2984–2996.

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