Tissue-specific heteroplasmy segregation is accompanied by a sharp mtDNA decline in Caenorhabditis elegans soma

Nikita Tsyba; Gaomin Feng; Lantana K Grub; James P Held; Adrianna M Strozak; Kristopher Burkewitz; Maulik R Patel

doi:10.1016/j.isci.2023.106349

Tissue-specific heteroplasmy segregation is accompanied by a sharp mtDNA decline in Caenorhabditis elegans soma

iScience. 2023 Mar 7;26(4):106349. doi: 10.1016/j.isci.2023.106349. eCollection 2023 Apr 21.

Authors

Nikita Tsyba¹, Gaomin Feng², Lantana K Grub¹, James P Held¹, Adrianna M Strozak¹, Kristopher Burkewitz², Maulik R Patel^{1

2

3

4}

Affiliations

¹ Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
² Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN37232, USA.
³ Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, TN37232, USA.
⁴ Evolutionary Studies, Vanderbilt University, Nashville, TN37235, USA.

Abstract

Mutations in the mitochondrial genome (mtDNA) can be pathogenic. Owing to the multi-copy nature of mtDNA, wild-type copies can compensate for the effects of mutant mtDNA. Wild-type copies available for compensation vary depending on the mutant load and the total copy number. Here, we examine both mutant load and copy number in the tissues of Caenorhabditis elegans. We found that neurons, but not muscles, have modestly higher mutant load than rest of the soma. We also uncovered different effect of aak-2 knockout on the mutant load in the two tissues. The most surprising result was a sharp decline in somatic mtDNA content over time. The scale of the copy number decline surpasses the modest shifts in mutant load, suggesting that it may exert a substantial effect on mitochondrial function. In summary, measuring both the copy number and the mutant load provides a more comprehensive view of the mutant mtDNA dynamics.

Keywords: Biological sciences; Cell biology; Molecular biology.

Abstract

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