The patient is a 35-year-old female who presents with complaints of fatigue. The patient’s past medical history is significant for deafness and ventricular tachycardia. Her family history is significant for similar symptoms in her mother.
Abnormalities of which of the following are seen in Figures #1 – #5?
A. Nuclei
B. Mitochondria
C. Lysosomes
D. T-tubules
The muscle fiber in center of this images shows increased finely granular to smudgy material between the sarcomeres and beneath the sarcolemma.
This material is nicely demonstrated with modified Gomori Trichrome stain in two other muscle fibers. Note the blue to bright magenta/red staining character.
Scattered muscle fibers show increased staining for succinic acid dehydrogenase (SDH), a protein encoded for by nuclear DNA (nDNA).
Scattered muscle fibers appear bright blue on combined succinic acid (SDH) and cytochrome oxidase (COX) enzyme histochemical stained sections. This is due to loss of brown COX staining, allowing the blue SDH stain to stand out. COX is encoded for by mitochondrial DNA (mtDNA).
EM shows abnormally enlarged shaped mitochondria (banana-like toward right half of image) and mitochondria containing paracrystalline inclusions. Not normal appearing mitochondria in background (small white arrows).
Correct Answer: Mitochondria
The features seen on light and electron microscopy reflect abnormalities of mitochondria. The appearance of the abnormal muscle fibers on modified Gomori Trichrome is also referred to as “ragged red muscle fibers.” The loss of COX staining is referred to as “COX-negative muscle fibers.” The paracrystalline inclusions seen on EM are also known as “parking lot” inclusions.
Of possible interest:
Your cells coordinate two genomes: nuclear DNA which follows Mendelian inheritance, and mitochondrial DNA (mtDNA) which does not follow Mendelian inheritance (I would suggest reading about homoplasmy, heteroplasmy, threshold, mtDNA copy number, variable dependence of different cells on mitochondrial energy production).
Your mitochondria are inherited from your mother.
Chloroplasts in plants also retain their own genomes.
Reference(s) / additional reading:
Fernandez-Vizarra E, Zeviani M. Mitochondrial disorders of the OXPHOS system. FEBS Lett. 2021 Apr;595(8):1062-1106. doi: 10.1002/1873-3468.13995. Epub 2020 Dec 18. PMID: 33159691.
Filograna R, Mennuni M, Alsina D, Larsson NG. Mitochondrial DNA copy number in human disease: the more the better? FEBS Lett. 2021 Apr;595(8):976-1002. doi: 10.1002/1873-3468.14021. Epub 2020 Dec 25. PMID: 33314045; PMCID: PMC8247411.
Russell OM, Gorman GS, Lightowlers RN, Turnbull DM. Mitochondrial Diseases: Hope for the Future. Cell. 2020 Apr 2;181(1):168-188. doi: 10.1016/j.cell.2020.02.051. Epub 2020 Mar 26. PMID: 32220313.
Rahman S. Mitochondrial disease in children. J Intern Med. 2020 Jun;287(6):609-633. doi: 10.1111/joim.13054. Epub 2020 Apr 7. PMID: 32176382.
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