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The Autophagy, Inflammation and Metabolism Center international eSymposium - an early-career investigators' seminar series during the COVID-19 pandemic

Jose L Nieto-Torres, Joanne Durgan, Anais Franco-Romero, Paolo Grumati, Carlos M Guardia, Andrew M Leidal, Michael A Mandell, Christina G Towers, Fei Wang

The Autophagy, Inflammation and Metabolism (AIM) Center organized a globally accessible, virtual eSymposium during the COVID-19 pandemic in 2020. The conference included presentations from scientific leaders, as well as a career discussion panel, and provided a much-needed platform for early-career investigators (ECIs) to showcase their research in autophagy. This Perspective summarizes the science presented by the ECIs during the event and discusses the lessons learned from a virtual meeting of this kind during the pandemic. The meeting was a learning experience for all involved, and the ECI participants herein offer their thoughts on the pros and cons of virtual meetings as a modality, either as standalone or hybrid events, with a view towards the post-pandemic world.

A Mammalian Target of Rapamycin Perilipin 3 (mTORC1-Plin3) Pathway
is essential to Activate Lipophagy and
Protects Against Hepatosteatosis

Marina Garcia-Macia et al

NAFLD is the most common hepatic pathology in western countries and no treatment is currently available. NAFLD is characterized by the aberrant hepatocellular accumulation of fatty acids in the form of lipid droplets (LDs). Recently, it was shown that liver LD degradation occurs through a process termed lipophagy, a form of autophagy. However, the molecular mechanisms governing liver lipophagy are elusive. Here, we aimed to ascertain the key molecular players that regulate hepatic lipophagy and their importance in NAFLD.

Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model

Adrián Santos-Ledo et al

Metabolic syndrome is a global health problem in adults and its prevalence among children and adolescents is rising. It is strongly linked to a lifestyle with high-caloric food, which causes obesity and lipid metabolism anomalies. Molecular damage due to excessive oxidative stress plays a major role during the development of metabolic syndrome complications. Among the different hormones, melatonin presents strong antioxidant properties, and it is used to treat metabolic diseases. However, there is not a consensus about its use as a metabolic syndrome treatment. The aim of this study was to identify melatonin effects in a metabolic syndrome model. Golden hamsters were fed with 60% fructose-enriched food to induce metabolic syndrome and were compared to hamsters fed with regular chow diet. Both groups were also treated with melatonin. Fructose-fed hamsters showed altered blood lipid levels (increased cholesterol and LDL) and phenotypes restored with the melatonin treatment. The Harderian gland (HG), which is an ideal model to study autophagy modulation through oxidative stress, was the organ that was most affected by a fructose diet. Redox balance was altered in fructose-fed HG, inducing autophagic activation. However, since LC3-II was not increased, the impairment must be in the last steps of autophagy. Lipophagy HG markers were also disturbed, contributing to the dyslipidemia. Melatonin treatment improved possible oxidative homeostasis through autophagic induction. All these results point to melatonin as a possible treatment of the metabolic syndrome.

Autophagy-targeted therapy to modulate age-related diseases: Success, pitfalls, and new directions

Waleska Kerllen Martins et al

Autophagy is a critical metabolic process that supports homeostasis at a basal level and is dynamically regulated in response to various physiological and pathological processes. Autophagy has some etiologic implications that support certain pathological processes due to alterations in the lysosomal-degradative pathway. Some of the conditions related to autophagy play key roles in highly relevant human diseases, e.g., cardiovascular diseases(15.5%), malignant and other neoplasms (9.4%), and neurodegenerative conditions (3.7%). Despite advances in the discovery of new strategies to treat these age-related diseases, autophagy has emerged as a therapeutic option after preclinical and clinical studies. Here, we discuss the pitfalls and success in regulating autophagy initiation and its lysosome-dependent pathway to restore its homeostatic role and mediate therapeutic effects for cancer, neurodegenerative, and cardiac diseases. The main challenge for the development of autophagy regulators for clinical application is the lack of specificity of the repurposed drugs, due to the low pharmacological uniqueness of their target, including those that target the PI3K/AKT/mTOR and AMPK pathway. Then, future efforts must be conducted to deal with this scenery, including the disclosure of key components in the autophagy machinery that may intervene in its therapeutic regulation. Among all efforts, those focusing on the development of novel allosteric inhibitors against autophagy inducers, as well as those targeting autolysosomal function, and their integration into therapeutic regimens should remain a priority for the field.

Autophagy wins the 2016 Nobel Prize in Physiology or Medicine

Beth Levine

On October 3, 2016, the Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for “discoveries of the mechanisms for autophagy.” Just a few weeks earlier, at an acceptance speech for the 2016 Paul Janssen Award, Yoshinori Ohsumi stated that although he performs research in a simple organism—baker’s yeast—he always hoped his research would have an impact upon human health. Indeed, Ohsumi’s discoveries, along with those of others working simultaneously on autophagy-related pathways in yeast, have provided a powerful molecular tool kit that thousands of scientists are now using worldwide to decipher the roles of autophagy in mammalian health and disease. The story of this year’s Nobel Prize represents a better-than-textbook example of why unbridled discovery in fundamental basic science is crucial for opening new frontiers in medicine.