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Lysosomal Signaling Promotes Longevity by Adjusting Mitochondrial Activity
- Source :
- Developmental Cell. 48:685-696.e5
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Summary 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 s-oxidation to reduce lipid storage and promote longevity in Caenorhabditis elegans. We further discovered that increased mitochondrial s-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.
- Subjects :
- media_common.quotation_subject
Longevity
Mitochondrion
medicine.disease_cause
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Escherichia coli
medicine
Animals
Homeostasis
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Molecular Biology
Transcription factor
030304 developmental biology
media_common
chemistry.chemical_classification
0303 health sciences
Reactive oxygen species
biology
Cell Biology
biology.organism_classification
Mitochondria
Cell biology
Oxidative Stress
chemistry
Chaperone (protein)
biology.protein
Signal transduction
Lysosomes
Reactive Oxygen Species
030217 neurology & neurosurgery
Oxidative stress
Molecular Chaperones
Transcription Factors
Developmental Biology
Subjects
Details
- ISSN :
- 15345807
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Developmental Cell
- Accession number :
- edsair.doi.dedup.....9f3ded3c50bee576c1073d4c977a5d7c