Functional respiratory chain studies in subjects with chronic progressive external ophthalmoplegia and large heteroplasmic mitochondrial DNA deletions

I Trounce; E Byrne; S Marzuki; X Dennett; H Sudoyo; F Mastaglia; S F Berkovic

doi:10.1016/0022-510x(91)90098-r

Functional respiratory chain studies in subjects with chronic progressive external ophthalmoplegia and large heteroplasmic mitochondrial DNA deletions

J Neurol Sci. 1991 Mar;102(1):92-9. doi: 10.1016/0022-510x(91)90098-r.

Authors

I Trounce¹, E Byrne, S Marzuki, X Dennett, H Sudoyo, F Mastaglia, S F Berkovic

Affiliation

¹ Mitochondrial Diseases Investigational Unit, St. Vincent's Hospital, Fitzroy, Australia.

PMID: 1677417
DOI: 10.1016/0022-510x(91)90098-r

Abstract

The functional consequences of large heteroplasmic mtDNA deletions were investigated in a group of 6 patients with chronic progressive external ophthalmoplegia (CPEO) syndromes. State III respiration rates corrected for age were low with site I and II substrates in all cases and cytochrome oxidase activity was depressed. The severity of impairment varied and is consistent with inclusion of a variable percentage of non-functioning mitochondria (with deleted mtDNA) in the pellet. Western blot studies with a holocomplex antibody battery revealed no abnormalities in subunit content of complexes III and IV. A deficiency of several complex I subunits in 3 cases suggests that abnormal nuclear-mitochondrial regulation of complex I assembly may follow large mtDNA deletions.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Chromosome Deletion
Cytochrome-c Oxidase Deficiency*
DNA, Mitochondrial / genetics*
Electron Transport
Electron Transport Complex III / deficiency*
Electron Transport Complex III / genetics
Electron Transport Complex IV / genetics
Female
Glutamates / metabolism
Glutamic Acid
Humans
Male
Middle Aged
Mitochondria / metabolism
NAD(P)H Dehydrogenase (Quinone)
Ophthalmoplegia / genetics
Ophthalmoplegia / metabolism*
Oxidative Phosphorylation
Oxygen Consumption
Pyruvates / metabolism
Pyruvic Acid
Quinone Reductases / deficiency*
Quinone Reductases / genetics
RNA, Transfer / genetics
Succinates / metabolism
Succinic Acid

Substances

DNA, Mitochondrial
Glutamates
Pyruvates
Succinates
Glutamic Acid
Pyruvic Acid
RNA, Transfer
Succinic Acid
NAD(P)H Dehydrogenase (Quinone)
Quinone Reductases
Electron Transport Complex IV
Electron Transport Complex III