Assessing mitochondrial dysfunction in cells

Abstract

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.

C-phycocyanin prevents cisplatin-induced mitochondrial dysfunction and oxidative stress

“…The main indicator of mitochondrial functionality is the RCR (states 3/4) as it expresses the coupling degree between the ETC and the ATP synthesis; a low value could indicate mitochondrial dysfunction which can be due to a failure in the mitochondrial membrane integrity and/or in the functionality of any of the mitochondrial complexes [52]. Another mitochondrial functionality indicator is the ADP/O ratio, which represents the number of ATP moles synthesized per mole of O 2 consumed [52].…”

“…Another mitochondrial functionality indicator is the ADP/O ratio, which represents the number of ATP moles synthesized per mole of O 2 consumed [52]. The CP-induced mitochondrial dysfunction was characterized by alterations in oxygen consumption rates, using as substrates both glutamate/malate and succinate, consequently causing a reduction in RCR, ATP synthesis, ADP/O ratio, calcium transport, and DW.…”

New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors

“…Induction of mPT is associated with caspase-dependent and caspase-independent cell death cascades in the central nervous system (Stavrovskaya et al 2004). Mitochondrial dysfunctions are usually related to the ability of the mitochondria to generate ATP in response to energy demands (Brand and Nicholls 2011). These processes may be amplified by increases in glutamate efflux in the prefrontal cortex and the hippocampus of depressed patients (Moghaddam 2002).…”

Sex differences in the regulation of spatially distinct cardiac mitochondrial subpopulations

“…As ATP/ADP exchange across the mitochondrial inner membrane is driven by membrane potential, a lower membrane potential could also contribute to less ATP/ADP exchange. Proton leak can also affect RCR; mitochondrial respiratory control encapsulates the main function of mitochondria: their ability to stay idle at a low rate yet respond to ADP by making ATP at a high rate [36]. A high RCR implies that the mitochondria have a high capacity for substrate oxidation and ATP turnover and a low proton leak.…”