Details

Autor(en) / Beteiligte

• Ramachandran, Prasanna V.
• Savini, Marzia
• Folick, Andrew K.
• Hu, Kuang
• Masand, Ruchi
• Graham, Brett H.
• Wang, Meng C.

Titel

Lysosomal Signaling Promotes Longevity by Adjusting Mitochondrial Activity

Ist Teil von

• Developmental cell, 2019-03, Vol.48 (5), p.685-696.e5

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Lysosomes and mitochondria are both crucial cellular organelles for metabolic homeostasis and organism health. However, mechanisms linking their metabolic activities to promote organism longevity remain poorly understood. We discovered that the induction of specific lysosomal signaling mediated by a LIPL-4 lysosomal acid lipase and its lipid chaperone LBP-8 increases mitochondrial ß-oxidation to reduce lipid storage and promote longevity in Caenorhabditis elegans. We further discovered that increased mitochondrial ß-oxidation reduces mitochondrial electron transport chain complex II activity, contributing to the induction of reactive oxygen species in mitochondria (mtROS) and the longevity effect conferred by LIPL-4–LBP-8 signaling. Moreover, by activating the JUN-1 transcription factor downstream of mtROS, the LIPL-4–LBP-8 signaling pathway induces antioxidant targets and oxidative stress tolerance. Together, these results reveal regulatory mechanisms by which lysosomal signaling triggers adjustments in mitochondrial activity and suggest the significance of these metabolic adjustments for improving metabolic fitness, redox homeostasis, and longevity. [Display omitted] •Lysosomal lipid messenger signaling actively regulates mitochondrial ß-oxidation•Mitochondrial ß-oxidation modulates electron transport chain complex II activity•Lysosomal and mitochondrial pro-longevity signaling converge on JUN-1•Organelle coordination improves metabolic balance, redox homeostasis, and longevity Ramachandran et al. uncover in C. elegans metabolic and signaling inter-organelle communication between lysosomes, mitochondria, and the nucleus. They demonstrate a crucial role for lysosomal lipid messenger signaling to actively trigger adjustments in mitochondrial activity that in turn coordinate lipid metabolism, redox homeostasis, and longevity.