Open AccessAging shifts mitochondrial dynamics toward fission to promote germline stem cell loss
Author(s) -
Amartuvshin Oyundari,
Lin ChiHung,
Hsu ShaoChun,
Kao ShihHan,
Chen Alvin,
Tang WeiChun,
Chou HanLin,
Chang DongLin,
Hsu YenYang,
Hsiao BaiShiou,
Rastegari Elham,
Lin KunYang,
Wang YuTing,
Yao ChiKuang,
Chen GuangChao,
Chen BiChang,
Hsu HweiJan
Publication year - 2020
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13191
Subject(s) - mitochondrial fission , biology , microbiology and biotechnology , mitochondrial fusion , stem cell , mitochondrion , germline , dnm1l , dnaja3 , mitochondrial dna , genetics , gene
Changes in mitochondrial dynamics (fusion and fission) are known to occur during stem cell differentiation; however, the role of this phenomenon in tissue aging remains unclear. Here, we report that mitochondrial dynamics are shifted toward fission during aging of Drosophila ovarian germline stem cells (GSCs), and this shift contributes to aging‐related GSC loss. We found that as GSCs age, mitochondrial fragmentation and expression of the mitochondrial fission regulator, Dynamin‐related protein (Drp1), are both increased, while mitochondrial membrane potential is reduced. Moreover, preventing mitochondrial fusion in GSCs results in highly fragmented depolarized mitochondria, decreased BMP stemness signaling, impaired fatty acid metabolism, and GSC loss. Conversely, forcing mitochondrial elongation promotes GSC attachment to the niche. Importantly, maintenance of aging GSCs can be enhanced by suppressing Drp1 expression to prevent mitochondrial fission or treating with rapamycin, which is known to promote autophagy via TOR inhibition. Overall, our results show that mitochondrial dynamics are altered during physiological aging, affecting stem cell homeostasis via coordinated changes in stemness signaling, niche contact, and cellular metabolism. Such effects may also be highly relevant to other stem cell types and aging‐induced tissue degeneration.