Ragged red fibers: Mitochondrial disorders

Ragged red fibers:Mitochondrial disorders

Mitochondrial disorders are accompanied by a massive proliferation and enlargement of mitochondria in myofibers. On electron microscopic examination, these mitochondria are large and structurally abnormal. 
They have a concentric or other unusual arrangement of their cristae and some of them contain crystal-like inclusions.

Ragged red fibres

Myofibers with such deposits are called ragged red fibers (RRFs)-ragged because their structure is disrupted by the accumulating mitochondria. RRFs are the hallmark of mitochondrial disorders and occur in no other metabolic disease but are only present in about one-third of them. 
They may be few or may be the majority of myofibers in a biopsy. Thus absence of RRFs does not rule out a mitochondrial disorder. RRFs occur in large deletions and tRNA mutations and in mutations of nDNA that cause multiple mtDNA deletions or reduction of mtDNA copy number. The common denominator of these conditions is impairment of intramitochondrial protein synthesis. 
They are less abundant or absent in mutations involving protein-coding genes. RRFs are Succinic Dehydrogenase (SDH) and NADH hyperreactive. The SDH reaction product is deep blue, hence RRFs are also ragged blue fibers. SDH (complex II) is entirely encoded by nDNA and a good marker of mitochondrial proliferation. Cytochrome C Oxidase (COX) is a component of complex IV which is encoded in part by mtDNA and in part by nDNA. COX is synthesized in mitochondria and reflects respiratory chain function. Therefore, RRFs in mutations affecting protein synthesis are deficient in COX activity. RRFs occurring in mutations of individual respiratory chain genes (except for those that encode COX components) are generally COX-positive. RRFs are rare in children with mitochondrial disorders and occur in other muscle diseases-notably inclusion body myositis and polymyalgia rheumatica. In these conditions, they are thought to be due to mtDNA damage induced by free radicals. A few RRFs are also seen incidentally in the muscles of older people. Milder mitochondrial proliferation often takes the form of subsarcolemmal aggregates that do not disrupt myofiber structure.

https://viral481.com/srv.html?id=5489389&pub=1009655

https://viral481.com/srv.html?id=5489410&pub=1009655