Uzhachenko 2017 Aging (Albany NY)
| Uzhachenko R, Boyd K, Olivares-Villagomez D, Zhu Y, Goodwin JS, Rana T, Shanker A, Tan WJ, Bondar T, Medzhitov R, Ivanova AV (2017) Mitochondrial protein Fus1/Tusc2 in premature aging and age-related pathologies: critical roles of calcium and energy homeostasis. Aging (Albany NY) 9:627-49. |
Uzhachenko R, Boyd K, Olivares-Villagomez D, Zhu Y, Goodwin JS, Rana T, Shanker A, Tan WJ, Bondar T, Medzhitov R, Ivanova AV (2017) Aging (Albany NY)
Abstract: Decreased energy production and increased oxidative stress are considered to be major contributors to aging and aging-associated pathologies. The role of mitochondrial calcium homeostasis has also been highlighted as an important factor affecting different pathological conditions. Here, we present evidence that loss of a small mitochondrial protein Fus1 that maintains mitochondrial homeostasis results in premature aging, aging-associated pathologies, and decreased survival. We showed that Fus1KO mice develop multiple early aging signs including lordokyphosis, lack of vigor, inability to accumulate fat, reduced ability to tolerate stress, and premature death. Other prominent pathological changes included low sperm counts, compromised ability of adult stem cells to repopulate tissues, and chronic inflammation. At the molecular level, we demonstrated that mitochondria of Fus1 KO cells have low reserve respiratory capacity (the ability to produce extra energy during sudden energy demanding situations), and show significantly altered dynamics of cellular calcium response. Our recent studies on early hearing and memory loss in Fus1 KO mice combined with the new data presented here suggest that calcium and energy homeostasis controlled by Fus1 may be at the core of its aging-regulating activities. Thus, Fus1 protein and Fus1-dependent pathways and processes may represent new tools and targets for anti-aging strategies.
• Bioblast editor: Kandolf G
Labels: MiParea: Respiration, mtDNA;mt-genetics
Pathology: Aging;senescence
Stress:Oxidative stress;RONS
Organism: Mouse
Tissue;cell: Kidney, Endothelial;epithelial;mesothelial cell, Fibroblast
Regulation: Calcium
Coupling state: LEAK, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
Pathway: ROX
HRR: Oxygraph-2k
Labels, 2017-07
