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Published on: November 30, 2022
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The RAB27A effector SYTL5 regulates mitophagy and mitochondrial metabolism
Ana Lapão1,2, Lauren Sophie Johnson1,2,3, Laura Trachsel-Moncho1,2,3
1Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Elife
|November 26, 2025
Summary
Synaptotagmin-Like 5 (SYTL5) acts as a RAB27A effector, playing a crucial role in mitophagy. Reduced SYTL5 expression in adrenal tumors correlates with patient survival, suggesting its potential as a biomarker.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Synaptotagmin-Like (SYTL) proteins are involved in membrane transport, but the specific function of SYTL5 is unknown.
- SYTL5 possesses a unique N-terminal domain interacting with the small GTPase RAB27A.
Purpose of the Study:
- To elucidate the function of SYTL5.
- To investigate the role of SYTL5 and RAB27A in cellular processes, particularly mitophagy.
- To explore the clinical relevance of SYTL5 in adrenocortical carcinoma.
Main Methods:
- Investigated SYTL5-RAB27A interaction and localization.
- Analyzed vesicle formation under hypoxia and effects of SYTL5/RAB27A depletion on mitophagy.
- Assessed mitochondrial respiration, glucose uptake, and SYTL5 expression in tumor samples.
Main Results:
- SYTL5 is a RAB27A effector, co-localizing with RAB27A on mitochondria and vesicles containing mitochondrial material.
- SYTL5-RAB27A mediated vesicle formation during hypoxia is essential for mitophagy; depletion impairs this process.
- SYTL5 depletion compromises mitochondrial respiration and increases glucose uptake; reduced SYTL5 expression correlates with better survival in adrenocortical carcinoma patients.
Conclusions:
- SYTL5, as a RAB27A effector, plays a significant role in hypoxia-induced mitophagy.
- SYTL5 influences mitochondrial function and cellular metabolism.
- SYTL5 is a potential prognostic biomarker in adrenocortical carcinoma.
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