Mitochondria, brain aging and neurodegenerative disorders

Toledano, A

doi:10.1007/bf03324203

Cited by 1 publication

(1 citation statement)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the nineties, it was already evident that mitochondria were at the center stage of diseases related to aging. [1][2][3] On addressing "mitochondrial encephalomyopathies" DiMauro and Moraes [4] described a group of disorders caused by biochemical alterations that included a decrease in the activity of diverse TCA cycle enzymes, aconitase, fumarase, or the dihydrolipoyl transferase unit of the α-ketoglutarate dehydrogenase complex. Although the underlying mechanisms are unknown, there is now consensus that the altered functioning of the mitochondria is behind neuronal death in neurodegenerative diseases.…”

Section: How Mitochondrial Energy Metabolism Impacts On Cell Survivalmentioning

confidence: 99%

The unbroken Krebs cycle. Hormonal‐like regulation and mitochondrial signaling to control mitophagy and prevent cell death

Franco

Serrano-Marín

2022

BioEssays

View full text Add to dashboard Cite

The tricarboxylic acid (TCA) or Krebs cycle, which takes place in prokaryotic cells and in the mitochondria of eukaryotic cells, is central to life on Earth and participates in key events such as energy production and anabolic processes. Despite its relevance, it is not perceived as tightly regulated compared to other key metabolisms such as glycolysis/gluconeogenesis. A better understanding of the functioning of the TCA cycle is crucial due to mitochondrial function impairment in several diseases, especially those that occur with neurodegeneration. This article revisits what is known about the regulation of the Krebs cycle and hypothesizes the need for large‐scale, rapid regulation of TCA cycle enzyme activity. Evidence of mitochondrial enzyme activity regulation by activation/deactivation of protein kinases and phosphatases exists in the literature. Apart from indirect regulation via G protein‐coupled receptors (GPCRs) at the cell surface, signaling upon activation of GPCRs in mitochondrial membranes may lead to a direct regulation of the enzymes of the Krebs cycle. Hormonal‐like regulation by posttranscriptional events mediated by activable kinases and phosphatases deserve proper assessment using isolated mitochondria. Also see the video abstract here: https://youtu.be/aBpDSWiMQyI

show abstract