Respiratory supercomplexes plasticity and implications

Porras, Christina Ann-Marie; Bai, Yidong

doi:10.2741/4327

Cited by 33 publications

(9 citation statements)

References 91 publications

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“…Taken together, the results from the OXPHOS Western blot and the dynamic metabolic measurements from the Seahorse suggest that there is not a decrease in expression of OXPHOS complexes in older cortical neuron mitochondria but instead a dysfunction of respiration and energy metabolism in the existing ETC. Indeed, it is possible that the assembly of respiratory complexes or supercomplexes is impaired [ 63 ]. Further investigation of each OXPHOS complex and their enzymatic activity in cortical neurons (as previously analyzed in isolated mitochondria from whole brain tissue [ 62 ]) would be helpful to answer the questions raised by these results.…”

Section: Discussionmentioning

confidence: 99%

Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Sutherland

Sefiani

Horvat

et al. 2021

Cells

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The age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating axon growth after injury, the impact of aging is still unknown. Mitochondria are essential to successful neurite and axon growth, while aging is associated with a decline in mitochondrial functions. Using isolation and culture of adult cortical neurons, we analyzed mitochondrial changes in 2-, 6-, 12- and 18-month-old mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however, mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest that dysfunctional mitochondria in older neurons may be associated with the age-dependent reduction in neurite growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can combine to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.

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Section: Discussionmentioning

confidence: 99%

Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Sutherland

Sefiani

Horvat

et al. 2021

Cells

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“…The electron transport chain (ETC) comprises five complexes (I-V) that regulate the transfer of nicotinamide adenine dinucleotide (NADH) and succinate through the ETC, and the generation of an electrochemical gradient across the inner mitochondrial membrane to drive ATP synthase (complex V). Respiratory activity is determined by the assembly of respiratory chain complexes into functional supercomplexes within the inner mitochondrial membrane (Cogliati et al 2013), although single complexes are also believed to exist to enable flexibility and adaptation to environmental changes (Porras & Bai 2015). The environment created within the inner mitochondrial membrane is distinct from the cytosol (Tzagoloff 1982, Herrmann & Riemer 2010, hence the mitochondrion possesses shuttles which regulate specific metabolite levels between the cytoplasm and the mitochondria and contribute to metabolic homeostasis (Herrmann & Riemer 2010, Wang et al 2014.…”

Section: Mitochondrial Function and Cellular Homeostasismentioning

confidence: 99%

Mitochondria in early development: linking the microenvironment, metabolism and the epigenome

Harvey¹

2019

Reproduction

117

101

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Mitochondria, originally of bacterial origin, are highly dynamic organelles that have evolved a symbiotic relationship within eukaryotic cells. Mitochondria undergo dynamic, stage-specific restructuring and redistribution during oocyte maturation and preimplantation embryo development, necessary to support key developmental events. Mitochondria also fulfil a wide range of functions beyond ATP synthesis, including the production of intracellular reactive oxygen species and calcium regulation, and are active participants in the regulation of signal transduction pathways. Communication between not only mitochondria and the nucleus, but also with other organelles, is emerging as a critical function which regulates preimplantation development. Significantly, perturbations and deficits in mitochondrial function manifest not only as reduced quality and/or poor oocyte and embryo development but contribute to post-implantation failure, long-term cell function and adult disease. A growing body of evidence indicates that altered availability of metabolic co-factors modulate the activity of epigenetic modifiers, such that oocyte and embryo mitochondrial activity and dynamics have the capacity to establish long-lasting alterations to the epigenetic landscape. It is proposed that preimplantation embryo development may represent a sensitive window during which epigenetic regulation by mitochondria is likely to have significant short- and long-term effects on embryo, and offspring, health. Hence, mitochondrial integrity, communication and metabolism are critical links between the environment, the epigenome and the regulation of embryo development.

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“…Complex I binds to a number of NAD-linked dehydrogenases in the mitochondrial matrix such as pyruvate dehydrogenase, but not malate or glutamate dehydrogenase 31 . Furthermore, supercomplexes are formed between respiratory complexes I, III and IV, whereas the involvement of complex II in supercomplexes is controversial 32–34 . The structural association of dehydrogenases to complex I, and thus to complexes III and IV, causes the formation of a so-called „metabolome“, where the electrons pass straight from the dehydrogenase and through the electron transport chain 34 .…”

Section: Discussionmentioning

confidence: 99%

Respiration of permeabilized cardiomyocytes from mice: no sex differences, but substrate-dependent changes in the apparent ADP-affinity

Karro

Laasmaa

Vendelin

et al. 2019

Sci Rep

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Sex differences in cardiac physiology are getting increased attention. This study assessed whether isolated, permeabilized cardiomyocytes from male and female C57BL/6 mice differ in terms of their respiration with multiple substrates and overall intracellular diffusion restriction estimated by the apparent ADP-affinity of respiration. Using respirometry, we recorded 1) the activities of respiratory complexes I, II and IV, 2) the respiration rate with substrates fuelling either complex I, II, or I + II, and 3) the apparent ADP-affinity with substrates fuelling complex I and I + II. The respiration rates were normalized to protein content and citrate synthase (CS) activity. We found no sex differences in CS activity (a marker of mitochondrial content) normalized to protein content or in any of the respiration measurements. This suggests that cardiomyocytes from male and female mice do not differ in terms of mitochondrial respiratory capacity and apparent ADP-affinity. Pyruvate modestly lowered the respiration rate, when added to succinate, glutamate and malate. This may be explained by intramitochondrial compartmentalization caused by the formation of supercomplexes and their association with specific dehydrogenases. To our knowledge, we show for the first time that the apparent ADP-affinity was substrate-dependent. This suggests that substrates may change or regulate intracellular barriers in cardiomyocytes.

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Respiratory supercomplexes plasticity and implications

Cited by 33 publications

References 91 publications

Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Mitochondria in early development: linking the microenvironment, metabolism and the epigenome

Respiration of permeabilized cardiomyocytes from mice: no sex differences, but substrate-dependent changes in the apparent ADP-affinity

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