Tsyba Nikita, Feng Gaomin, Grub Lantana K, Held James P, Strozak Adrianna M, Burkewitz Kristopher, Patel Maulik R
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN37232, USA.
iScience. 2023 Mar 7;26(4):106349. doi: 10.1016/j.isci.2023.106349. eCollection 2023 Apr 21.
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 . We found that neurons, but not muscles, have modestly higher mutant load than rest of the soma. We also uncovered different effect of 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.
线粒体基因组（mtDNA）中的突变可能具有致病性。由于mtDNA的多拷贝性质，野生型拷贝可以补偿突变型mtDNA的影响。可用于补偿的野生型拷贝数量因突变负荷和总拷贝数而异。在这里，我们研究了[具体生物名称]组织中的突变负荷和拷贝数。我们发现，神经元而非肌肉的突变负荷略高于躯体的其他部分。我们还发现敲除[具体基因名称]对这两种组织中的突变负荷有不同影响。最令人惊讶的结果是，随着时间的推移，体细胞mtDNA含量急剧下降。拷贝数下降的幅度超过了突变负荷的适度变化，这表明它可能对线粒体功能产生重大影响。总之，同时测量拷贝数和突变负荷能更全面地了解突变型mtDNA的动态变化。
