Assessing mitochondrial dysfunction in cells

Autor: David G. Nicholls, Martin D. Brand
Rok vydání: 2011
Předmět:
Mitochondrial Diseases
Cell
TMRM
tetramethylrhodamine methyl ester

Review Article
Mitochondrion
Biochemistry
0302 clinical medicine
Correction Article
mitochondrion
RCR
respiratory control ratio (state 3/state 4)

Membrane potential
0303 health sciences
PMPI
plasma membrane potential indicator

Δψp
plasma membrane potential

Δψm
mitochondrial membrane potential

TPP
tetraphenylphosphonium

Mitochondria
UQ
ubiquinone

FCCP
carbonyl cyanide p-trifluoromethoxyphenylhydrazone

medicine.anatomical_structure
030220 oncology & carcinogenesis
respiratory control
Protons
Respiration rate
Respiratory rate
Cells
Biology
Models
Biological

pmf
protonmotive force

Electron Transport
03 medical and health sciences
mitochondrial function
In vivo
Respiration
medicine
Animals
Humans
ΔpH
pH gradient

Molecular Biology
030304 developmental biology
Clinical Laboratory Techniques
R123
rhodamine 123

Cell Biology
state 3u
uncoupled state

state 4o
state 4oligomycin

Electron transport chain
TPMP
triphenylmethylphosphonium

Biophysics
membrane potential
Energy Metabolism
030217 neurology & neurosurgery
respiration
Zdroj: Biochemical Journal
ISSN: 1470-8728
Popis: Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands. Where other functions are of interest, tailored solutions are required. Dysfunction can be assessed in isolated mitochondria, in cells or in vivo, with different balances between precise experimental control and physiological relevance. There are many methods to measure mitochondrial function and dysfunction in these systems. Generally, measurements of fluxes give more information about the ability to make ATP than do measurements of intermediates and potentials. For isolated mitochondria, the best assay is mitochondrial respiratory control: the increase in respiration rate in response to ADP. For intact cells, the best assay is the equivalent measurement of cell respiratory control, which reports the rate of ATP production, the proton leak rate, the coupling efficiency, the maximum respiratory rate, the respiratory control ratio and the spare respiratory capacity. Measurements of membrane potential provide useful additional information. Measurement of both respiration and potential during appropriate titrations enables the identification of the primary sites of effectors and the distribution of control, allowing deeper quantitative analyses. Many other measurements in current use can be more problematic, as discussed in the present review.
Databáze: OpenAIRE