Mitochondria and the autophagy-inflammation-cell death axis in organismal aging

By Douglas R. Green, L. Galluzzi, Guido Kroemer. Science, 2011

1,198 citations recorded by the source corpus.

Alterations of mitochondrial functions are linked to multiple degenerative or acute diseases. As mitochondria age in our cells, they become progressively inefficient and potentially toxic, and acute damage can trigger the permeabilization of mitochondrial membranes to initiate apoptosis or necrosis. Moreover, mitochondria have an important role in pro-inflammatory signaling. Autophagic turnover of cellular constituents, be it general or specific for mitochondria (mitophagy), eliminates dysfunctional or damaged mitochondria, thus counteracting degeneration, dampening inflammation, and preventing unwarranted cell loss. Decreased expression of genes that regulate autophagy or mitophagy can cause degenerative diseases in which deficient quality control results in inflammation and the death of cell populations. Thus, a combination of mitochondrial dysfunction and insufficient autophagy may contribute to multiple aging-associated pathologies.

Subfields: Epidemiology, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/3af9a27495bad9e724d03715d09938960004239d

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Citations in the corpus

To be or not to be? How selective autophagy and cell death govern cell fate. (2014, positive): “…of reactive oxygen species (leading to genomic instability and enhanced proinflammatory signaling) —contribute to cancer, neurodegenerative diseases, myopathies, aging, and inflammatory disorders (reviewed in Ding and Yin, 2012; Green et al., 2011; Lu et al., 2013; Narendra and Youle, 2011).”
The hallmarks of aging. (2013, background): “…deficiencies may affect apoptotic signaling by increasing the propensity of mitochondria to permeabilize in response to stress (Kroemer et al., 2007) and trigger inflammatory reactions by favoring ROS-mediated and/or permeabilization-facilitated activation of inflammasomes (Green et al., 2011).”
Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles (2017, neutral): “↓ Mitophagy ↓ VPS34 ↓ ULK1 ↓ ROS ↓ ATG4B ↓ AMPK ↓ mTORC1 ↑ AMPK? ↑ ROS ↑ MAPK? ↑ BECN1 ↓ Ins(1,4,5)P3”
The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction. (2012, neutral): “sequent accumulation of dysfunctional, reactive oxygen species– generating mitochondria renders cells more sensitive to apoptotic and inflammatory stimuli (Terman et al., 2010; Green et al., 2011; Nakahira et al., 2011; Zhou et al., 2011).”
Mitophagy: mechanisms, pathophysiological roles, and analysis (2012, background): “Drp1 is a cytosolic protein, but it can be recruited to the surface of mitochondria where it interacts with a partner protein, mitochondrial fi ssion 1 (Fis1), through the adaptor proteins Mdv1 and Caf4 to trigger mitochondrial fi ssion in yeast (Griffi n et al. , 2005 ; Westermann , 2010 ).”
Autophagy in malignant transformation and cancer progression (2015, positive): “In physiological scenarios, autophagy proceeds at basal levels, ensuring the continuous removal of superfluous, ectopic or damaged (and hence potentially dangerous) entities, including organelles and/or portions thereof (Green et al , 2011).”
Comprehending crystalline β-carotene accumulation by comparing engineered cell models and the natural carotenoid-rich system of citrus (2011, neutral): “In many other organisms, mitochondrial function is highly involved in various cellular processes influenced by environmental conditions (Lee et al., 2002; Atkin and Macherel, 2009; Green et al., 2011; Gleason et al., 2011; Yang et al., 2011; Schwarzländer et al., 2012).”
Decoding cell death signals in liver inflammation. (2013, background): “24 mitophagy) can be initiated by MOMP and often involves a well characterized signal transduction pathway centered on the interaction between parkin and PTEN-induced putative kinase 1 (PINK1), two proteins that are mutated in familial Parkinson’s disease [33].”
A Unified Theory of Sepsis-Induced Acute Kidney Injury: Inflammation, microcirculatory dysfunction, bioenergetics and the tubular cell adaptation to injury (2014, neutral): “dicating that mitochondria are intimately involved in the regulation of the cell cycle (56).”
Defective Mitophagy in XPA via PARP1 Hyperactivation and NAD+/SIRT1 Reduction (2014, background): “As the power center of cells, mitochondria are involved in a plethora of metabolic networks and play a significant role in sustaining the life and health of humans (Green et al., 2011).”
Metabolic control of cell death (2014, background): “Macroautophagy (herein referred to as autophagy) is a major mechanism for the maintenance of intracellular homeostasis that can be dramatically up-regulated by nutrient deprivation and organellar damage (12, 58).”
Canonical Nlrp3 inflammasome links systemic low grade inflammation to functional decline in aging (2013, positive): “…in multiple organs, including adipose tissue and CNS, is postulated to be a common mechanism leading to several chronic degenerative disorders that negatively impacts the healthspan of the elderly (Lumeng et al., 2011; Green et al., 2011; Ferrucci et al., 2005; Franceschi et al., 2007).”