The Cell Non-Autonomous Nature of Electron Transport Chain-Mediated Longevity

By Jenni Durieux, Suzanne C Wolff, A. Dillin. Cell, 2011

1,053 citations recorded by the source corpus.

Summary The life span of C. elegans can be increased via reduced function of the mitochondria; however, the extent to which mitochondrial alteration in a single, distinct tissue may influence aging in the whole organism remains unknown. We addressed this question by asking whether manipulations to ETC function can modulate aging in a cell non-autonomous fashion. We report that the alteration of mitochondrial function in key tissues is essential for establishing and maintaining a pro-longevity cue. We find that regulators of mitochondrial stress responses are essential and specific genetic requirements for the electron transport chain (ETC) longevity pathway. Strikingly, we find that mitochondrial perturbation in one tissue is perceived and acted upon by the mitochondrial stress response pathway in a distal tissue. These results suggest that mitochondria may establish and perpetuate the rate of aging for the whole organism independent of cell-autonomous functions.

Subfields: Aging, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a2a73d881bf4bec0bce1bcb6e3369be49c69a67b

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Citations in the corpus

Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging (2013, background): “HIF-1α modulation may have differential effects on lifespan depending on the animal’s diet or whether the mtUPR is activated (Dillin et al., 2002; Durieux et al., 2011; Houtkooper et al., 2013).”
Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling (2018, neutral): “In fact, in C. elegans, conditions of increased ROS generation such as ETC dysfunction, loss of sod-2, PQ treatment, and reduced glucose metabolism were shown to promote longevity (Schulz et al., 2007; Durieux et al., 2011; Wang and Hekimi, 2015).”
Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals (2017, background): “…apparent contradiction, such as the requirement of additional regulatory components, like epigenetic modifications or non–cell-autonomous factors (Durieux et al., 2011; Merkwirth et al., 2016; Tian et al., 2016), as well as particular specificities of given cells, tissues, or stressors to…”
TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO (2012, background): “Life span of the skn-1; daf-16 mutant was unaffected by raga-1 RNAi but increased by inhibition of mitochondrial genes (cco-1, cyc-1; Tables S3 and S4), which involves a distinct longevity pathway (Durieux et al., 2011; Kenyon, 2010).”
The hallmarks of aging. (2013, background): “Hormetic reactions may trigger a mitochondrial defensive response both in the same tissue in which mitochondria are defective and even in distant tissues, as shown in C. elegans (Durieux et al., 2011).”
Mitochondrial ROS signaling in organismal homeostasis. (2015, background): “elegans downstream of ETC disruption and mtROS (Durieux et al., 2011; Schieber and Chandel, 2014) will be important to consider.”
The Mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance (2015, background): “…elegans, a stress-induced tissue-specific signal originating from mitochondria has been shown to communicate with distant organs and extend lifespan; the exact identity of this signal, termed ‘‘mitokine,’’ is unknown and currently being investigated (Durieux et al., 2011; Woo and Shadel, 2011).”
The Mitochondrial Basis of Aging (2016, background): “The link between the UPRmt and lifespan was made initially in the setting of attempting to explain why mutant worms, such as Molecular Cell 61, March 3, 2016 ª2016 Elsevier Inc. 657 those with knockdown of cco-1, live longer (Durieux et al., 2011).”
Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. (2013, background): “Recent studies 416 Cell Metabolism 18, 416–430, September 3, 2013 ª2013 Elsevie in worms and flies have also suggested that systemic interplay between multiple tissues regulates aging and longevity (Demontis and Perrimon, 2010; Durieux et al., 2011).”
NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus (2015, background): “Mitonuclear protein imbalance can be defined as a stoichiometric difference between nuclear and mitochondrial-encoded respiratory subunit proteins (Houtkooper et al., 2013), an effect known to promote longevity in worms (Durieux et al., 2011; Houtkooper et al., 2013).”