The Reindeer's Secret: Salazinic Acid from Lichens as a Candidate Modulator of Autophagy.
6 affiliations
- 1Center for Bio- and Medical Technologies, 121205 Moscow, Russia.
- 2Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
- 3Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia.
- 4Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, 117997 Moscow, Russia.
- 5Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia.
- 6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Abstract
Autophagy is a conserved lysosome-dependent process essential for cellular homeostasis, and pharmacological activation of autophagy has emerged as a promising therapeutic strategy for age-related, neurodegenerative, metabolic, and malignant diseases. Despite the growing interest in natural autophagy modulators, lichens remain largely unexplored as a source of autophagy-inducing compounds. Here, we tested ethanolic extracts from four commercially available lichens using LC3-II accumulation as a primary readout. Usnea sp. was identified as the most active species. Activity-guided fractionation followed by HRMS and NMR analyses identified salazinic acid as the active metabolite. Salazinic acid increased LC3-II accumulation, enhanced autophagic flux in the presence of bafilomycin A1, and promoted autophagosome formation as confirmed by transmission electron microscopy. The compound exhibited low cytotoxicity in human cell lines at concentrations exceeding those required for autophagy induction. Mechanistically, salazinic acid activated the phosphorylation of AMPK, ULK1, and AKT; however, it retained its ability to stimulate autophagic flux in AMPK- and ULK1-deficient cells, indicating that its activity is not strictly dependent on the canonical AMPK-ULK1 signaling pathway. Collectively, our findings identify salazinic acid as a previously unrecognized inducer of productive autophagic flux and demonstrate that lichen secondary metabolites represent a promising and largely untapped source of novel autophagy-modulating compounds.
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BibTeX
@article{veretina2026reindeers,
title = {{The Reindeer's Secret: Salazinic Acid from Lichens as a Candidate Modulator of Autophagy.}},
author = {Anastasiia K Veretina and Vera A Alferova and Ekaterina A Guseva and Anton R Izzi and Arina A Nikandrova and Gulnara K Kudryakova and Mikhail Y Zhitlov and Julia A Golubeva and Valeriya B Vays and Irina M Vangeli and Yulia M Khabibulina and Lora E Bakeeva and Anna A Lukianova and Lyamzaev G Konstantin and Dmitry S Karpov and Dmitrii A Lukianov and Olga A Dontsova and Petr V Sergiev},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198621},
url = {https://europepmc.org/article/MED/42883866},
note = {CC BY},
}
RIS
TY - JOUR
TI - The Reindeer's Secret: Salazinic Acid from Lichens as a Candidate Modulator of Autophagy.
AU - Anastasiia K Veretina
AU - Vera A Alferova
AU - Ekaterina A Guseva
AU - Anton R Izzi
AU - Arina A Nikandrova
AU - Gulnara K Kudryakova
AU - Mikhail Y Zhitlov
AU - Julia A Golubeva
AU - Valeriya B Vays
AU - Irina M Vangeli
AU - Yulia M Khabibulina
AU - Lora E Bakeeva
AU - Anna A Lukianova
AU - Lyamzaev G Konstantin
AU - Dmitry S Karpov
AU - Dmitrii A Lukianov
AU - Olga A Dontsova
AU - Petr V Sergiev
PY - 2026
DA - 2026/09/26
JO - International journal of molecular sciences
DO - 10.3390/ijms27198621
UR - https://europepmc.org/article/MED/42883866
AB - Autophagy is a conserved lysosome-dependent process essential for cellular homeostasis, and pharmacological activation of autophagy has emerged as a promising therapeutic strategy for age-related, neurodegenerative, metabolic, and malignant diseases. Despite the growing interest in natural autophagy modulators, lichens remain largely unexplored as a source of autophagy-inducing compounds. Here, we tested ethanolic extracts from four commercially available lichens using LC3-II accumulation as a primary readout. Usnea sp. was identified as the most active species. Activity-guided fractionation followed by HRMS and NMR analyses identified salazinic acid as the active metabolite. Salazinic acid increased LC3-II accumulation, enhanced autophagic flux in the presence of bafilomycin A1, and promoted autophagosome formation as confirmed by transmission electron microscopy. The compound exhibited low cytotoxicity in human cell lines at concentrations exceeding those required for autophagy induction. Mechanistically, salazinic acid activated the phosphorylation of AMPK, ULK1, and AKT; however, it retained its ability to stimulate autophagic flux in AMPK- and ULK1-deficient cells, indicating that its activity is not strictly dependent on the canonical AMPK-ULK1 signaling pathway. Collectively, our findings identify salazinic acid as a previously unrecognized inducer of productive autophagic flux and demonstrate that lichen secondary metabolites represent a promising and largely untapped source of novel autophagy-modulating compounds.
SN - 1422-0067
ER -