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Spectrum of combined respiratory chain defects.

Mayr JA, Haack TB, Freisinger P, Karall D, Makowski C, Koch J, Feichtinger RG, Zimmermann FA, Rolinski B, Ahting U, Meitinger T, Prokisch H, Sperl W - J. Inherit. Metab. Dis. (2015)

Bottom Line: Combined defects are found in 49 % of the known disease-causing genes of mitochondrial energy metabolism and in 57 % of patients with OXPHOS defects identified in our diagnostic centre.Defects in cofactors can result in combined defects of various combinations, and defects of mitochondrial homeostasis can result in a generalised decrease of all OXPHOS enzymes.Furthermore, even defects of single respiratory chain enzymes can result in combined defects due to aberrant formation of respiratory chain supercomplexes.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, Paracelsus Medical University, SALK Salzburg, Salzburg, 5020, Austria, H.Mayr@salk.at.

ABSTRACT
Inherited disorders of mitochondrial energy metabolism form a large and heterogeneous group of metabolic diseases. More than 250 gene defects have been reported to date and this number continues to grow. Mitochondrial diseases can be grouped into (1) disorders of oxidative phosphorylation (OXPHOS) subunits and their assembly factors, (2) defects of mitochondrial DNA, RNA and protein synthesis, (3) defects in the substrate-generating upstream reactions of OXPHOS, (4) defects in relevant cofactors and (5) defects in mitochondrial homeostasis. Deficiency of more than one respiratory chain enzyme is a common finding. Combined defects are found in 49 % of the known disease-causing genes of mitochondrial energy metabolism and in 57 % of patients with OXPHOS defects identified in our diagnostic centre. Combined defects of complexes I, III, IV and V are typically due to deficiency of mitochondrial DNA replication, RNA metabolism or translation. Defects in cofactors can result in combined defects of various combinations, and defects of mitochondrial homeostasis can result in a generalised decrease of all OXPHOS enzymes. Noteworthy, identification of combined defects can be complicated by different degrees of severity of each affected enzyme. Furthermore, even defects of single respiratory chain enzymes can result in combined defects due to aberrant formation of respiratory chain supercomplexes. Combined OXPHOS defects have a great variety of clinical manifestations in terms of onset, course severity and tissue involvement. They can present as classical encephalomyopathy but also with hepatopathy, nephropathy, haematologic findings and Perrault syndrome in a subset of disorders.

No MeSH data available.


Related in: MedlinePlus

Gene defects (n = 251) of mitochondrial energy metabolism associated with human disease. Gene defects that usually present as combined OXPHOS defects are highlighted in yellow (n = 123)
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Fig1: Gene defects (n = 251) of mitochondrial energy metabolism associated with human disease. Gene defects that usually present as combined OXPHOS defects are highlighted in yellow (n = 123)

Mentions: Mitochondria are cellular organelles essential for aerobic energy metabolism. Proper functioning of mitochondrial energy generation depends on numerous factors. It is assumed that more than 5 % of the human genome plays a role in this metabolism. Indeed, defects involving more than 250 genes (Fig. 1) have been identified to date, making disorders of mitochondrial energy metabolism the most heterogeneous metabolic disease group.Fig. 1


Spectrum of combined respiratory chain defects.

Mayr JA, Haack TB, Freisinger P, Karall D, Makowski C, Koch J, Feichtinger RG, Zimmermann FA, Rolinski B, Ahting U, Meitinger T, Prokisch H, Sperl W - J. Inherit. Metab. Dis. (2015)

Gene defects (n = 251) of mitochondrial energy metabolism associated with human disease. Gene defects that usually present as combined OXPHOS defects are highlighted in yellow (n = 123)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493854&req=5

Fig1: Gene defects (n = 251) of mitochondrial energy metabolism associated with human disease. Gene defects that usually present as combined OXPHOS defects are highlighted in yellow (n = 123)
Mentions: Mitochondria are cellular organelles essential for aerobic energy metabolism. Proper functioning of mitochondrial energy generation depends on numerous factors. It is assumed that more than 5 % of the human genome plays a role in this metabolism. Indeed, defects involving more than 250 genes (Fig. 1) have been identified to date, making disorders of mitochondrial energy metabolism the most heterogeneous metabolic disease group.Fig. 1

Bottom Line: Combined defects are found in 49 % of the known disease-causing genes of mitochondrial energy metabolism and in 57 % of patients with OXPHOS defects identified in our diagnostic centre.Defects in cofactors can result in combined defects of various combinations, and defects of mitochondrial homeostasis can result in a generalised decrease of all OXPHOS enzymes.Furthermore, even defects of single respiratory chain enzymes can result in combined defects due to aberrant formation of respiratory chain supercomplexes.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, Paracelsus Medical University, SALK Salzburg, Salzburg, 5020, Austria, H.Mayr@salk.at.

ABSTRACT
Inherited disorders of mitochondrial energy metabolism form a large and heterogeneous group of metabolic diseases. More than 250 gene defects have been reported to date and this number continues to grow. Mitochondrial diseases can be grouped into (1) disorders of oxidative phosphorylation (OXPHOS) subunits and their assembly factors, (2) defects of mitochondrial DNA, RNA and protein synthesis, (3) defects in the substrate-generating upstream reactions of OXPHOS, (4) defects in relevant cofactors and (5) defects in mitochondrial homeostasis. Deficiency of more than one respiratory chain enzyme is a common finding. Combined defects are found in 49 % of the known disease-causing genes of mitochondrial energy metabolism and in 57 % of patients with OXPHOS defects identified in our diagnostic centre. Combined defects of complexes I, III, IV and V are typically due to deficiency of mitochondrial DNA replication, RNA metabolism or translation. Defects in cofactors can result in combined defects of various combinations, and defects of mitochondrial homeostasis can result in a generalised decrease of all OXPHOS enzymes. Noteworthy, identification of combined defects can be complicated by different degrees of severity of each affected enzyme. Furthermore, even defects of single respiratory chain enzymes can result in combined defects due to aberrant formation of respiratory chain supercomplexes. Combined OXPHOS defects have a great variety of clinical manifestations in terms of onset, course severity and tissue involvement. They can present as classical encephalomyopathy but also with hepatopathy, nephropathy, haematologic findings and Perrault syndrome in a subset of disorders.

No MeSH data available.


Related in: MedlinePlus