Author(s)
Content
Video Abstract (AI generated) (01:20) Paper PreprintLysosomal acidification is a key feature of healthy cells. Inability to maintain lysosomal acidic pH is associated with aging and neurodegenerative diseases. However, the mechanisms elicited by impaired lysosomal acidification remain unknown. We show here that inhibition of lysosomal acidification triggers cellular iron deficiency, which results in impaired mitochondrial function and necrotic cell death. These effects are recovered by supplying iron via a lysosome-independent pathway. Notably, iron deficiency is sufficient to trigger inflammatory signaling in cultured primary neurons. Using a mouse model of impaired lysosomal acidification, we observed a robust iron deficiency response in the brain, verified by in vivo magnetic resonance imaging. Furthermore, the brains of these mice present a pervasive inflammatory signature associated with instability of mitochondrial DNA (mtDNA), both corrected by supplementation of the mice diet with iron. Our results highlight a novel mechanism linking lysosomal dysfunction, mitochondrial malfunction and inflammation in vivo.
More Projects
Loren Frank
13 views • 2 years ago
Global Immunotalks
390 views • 3 years ago
Laurel Yohe
2 views • 2 years ago
Global Immunotalks
130 views • 3 years ago
Jignesh H. Parmar
0 views • 2 years ago
Winston A. Haynes
0 views • 2 years ago
Noam Mazor
0 views • 2 years ago
Global Immunotalks
182 views • 3 years ago
Cem Yuksel
345 views • 3 years ago
Oscar Gonzalez-Recio
3 views • 2 years ago
Please pick a style:
Ira Milosevic. (2021, Nov 4).Impaired lysosomal acidification triggers iron deficiency, necrotic cell death and inflammation in vivo[Video]. Scitok. https://scitok.com/project/p/1581c638
Faisal Yambire King. "Impaired lysosomal acidification triggers iron deficiency, necrotic cell death and inflammation in vivo" Scitok, uploaded by Milosevic Ira, 4 Nov, 2021, https://scitok.com/project/p1581c638
Ira Milosevic. "Impaired lysosomal acidification triggers iron deficiency, necrotic cell death and inflammation in vivo" Scitok. (Nov 4, 2021). https://scitok.com/project/p/1581c638
Ira Milosevic (Nov 4, 2021). Impaired lysosomal acidification triggers iron deficiency, necrotic cell death and inflammation in vivo Scitok. https://scitok.com/project/p/1581c638
Ira Milosevic. Impaired lysosomal acidification triggers iron deficiency, necrotic cell death and inflammation in vivo[video]. 2021 Nov 4. https://scitok.com/project/p/1581c638
@online{al2006link, title={ Impaired lysosomal acidification triggers iron deficiency, necrotic cell death and inflammation in vivo }, author={ Milosevic, Ira }, organization={Scitok}, month={ Nov }, day={ 4 }, year={ 2021 }, url = {https://scitok.com/project/p/1581c638}, }