Details

Autor(en) / Beteiligte

• Carot, Alejandra Bargues
• Malovic, Emir
• Jin, Huajun
• Anantharam, Vellareddy
• Kanthasamy, Arthi
• Kanthasamy, Anumantha

Titel

Mitochondrial Impairment Upregulates MICOS Expression in a Human Microglial Cell Model

Ist Teil von

• The FASEB journal, 2019-04, Vol.33 (S1), p.lb19-lb19

Ort / Verlag

The Federation of American Societies for Experimental Biology

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Mitochondrial dysfunction and oxidative stress have been implicated as key pathological mechanisms underlying the dopaminergic neurodegenerative process of Parkinson's disease. The mitochondrial contact site and cristae‐organizing system (MICOS) complex, formed by two subcomplexes with a total of 7 subunits, is associated with the formation and maintenance of mitochondrial cristae structure and respiratory complexes as well as in the regulation of mitochondrial import machinery. Alterations of MICOS subunit protein levels, mutations, and protein modifications have been associated with distinct human diseases, including Parkinson's disease, diabetic cardiomyopathy, epilepsy, and cancer. Previous studies using the classic mitochondrial complex‐1 inhibitor rotenone have shown that overexpression of Mic60 attenuates the rotenone‐induced cell death and increased mitochondrial respiration and spare respiratory capacity in PC12 and SH‐SY5Y dopaminergic cell models. We recently reported that mitochondrial impairment in microglia amplifies the neuroinflammatory response in cell and animal models of rotenone‐induced neurotoxicity. To further understand the cellular mechanism underlying mitochondrial impairment and neuroinflammation, we investigated the effect of rotenone on MICOS subunits, specifically Mic27 and Mic60, in the novel C20 human microglia cell model. Our immunocytochemical, qPCR and Western blot analyses revealed that exposing C20 cells to rotenone for 24 hours induced the upregulation of Mic27 and Mic60. Microglia are known to be extremely resilient cells whose metabolic states differ greatly in comparison to neurons. Therefore, our future studies will determine if the upregulation of MICOS subunits in microglia represents a compensatory mechanism to relieve mitochondrial stress. Support or Funding Information (NIH grants NS100090, NS088206 and ES027245) This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.