Autophagy: mechanisms and applications—a session at the 20th IUPAB congress/45th SBBf annual meeting/50th SBBq annual meeting

Abstract

Autophagy is a conserved biological process used by cells to degrade and recycle components. Defects in autophagy are associated with multiple disease states, while interventions that promote autophagy may improve health. In a session at the 20th Congress of the International Union for Pure and Applied Biophysics (IUPAB), which was held along with the annual meetings of the Brazilian Society of Biophysics (SBBf) and the Brazilian Society of Biochemistry and Molecular Biology (SBBq), four speakers presented their studies linking autophagy to neurodegenerative diseases, heart failure, stress response, metabolism, and aging. They also proposed strategies to target autophagy as a way to ameliorate health.

Autophagy is a conserved process in which cells direct cytosolic components to lysosomes for degradation and recycling (Mizushima and Komatsu 2011; Parzych and Klionsky 2014). Diseases have been associated with defective autophagy, while interventions that ameliorate health have been shown to improve autophagy efficiency (Levine and Kroemer 2019). Autophagy varies depending on the mechanisms of cargo delivery to the lysosome and how selective these mechanisms are. While bulk autophagy is thought to be a homeostatic response to starvation, selective autophagy mediates the degradation of cellular components with high specificity.

In this session, I invited four speakers who presented their contribution to the understanding of the molecular processes underlying autophagy and its link to disease and age-related conditions (Fig. 1). This is in line with my general interest in mechanisms linking metabolism and aging (Guerra et al. 2019; Mori 2020).

Fig. 1.

Autophagy underlies the association between metabolism, disease and aging

Dr. Maho Hamasaki (Osaka University, Japan), whose research interests relies on identifying molecular mechanisms controlling autophagosome formation (Hamasaki et al. 2013; Nakamura et al. 2020), showed results with a new compound that binds to Atg16, promotes LC3-I to LC3-II conversion, and induces selective autophagy in mammalian cells and C. elegans. By doing so, the compound helps cells clear Salmonella infection and reduces polyglutamine aggregation. Consistent with a function alleviating proteotoxic burden, the compound also improves C. elegans mobility during aging.

Dr. Julio Ferreira (University of São Paulo, Brazil) studies the role of autophagy in cardiac and skeletal muscle mitochondrial quality control in conditions of heart failure and exercise (Campos et al. 2017, 2020). In his talk, he focused on a specific type of selective autophagy, called mitophagy, directed to damaged mitochondria. He showed that in a mouse model of heart failure, mitochondria are more fragmented, mitophagy is impaired, and there is accumulation of damaged mitochondria. In contrast, the use of compounds to block excessive mitochondrial fragmentation or to re-establish mitochondrial fusion protects from cardiac ischemia/reperfusion. He also linked changes in mitochondrial fusion to exercise performance and responsiveness in C. elegans and mice.

Dr. Louis R. Lapierre (Brown University, USA) researches the transcriptional and metabolic regulation of autophagy in aging (Seah et al. 2016; Silvestrini et al. 2018). He showed that sub-cellular compartmentalization of key components of the autophagic pathway serves as a regulatory step to control autophagy, connecting it to other metabolic pathways. He demonstrated that XPO-1 controls the nucleocytoplasmic shuttling of the transcription factor TFEB/HLH-30, which in turn influences the expression of autophagy-related genes and affects longevity in C. elegans. He also described how the selective autophagy receptor SQST-1/SQSTM1 is recruited to lipid droplets in response to inhibition of autophagy, concluding that lipid droplets buffer unstable proteins that could be targeted for selective autophagy, serving as an organelle for proteome stabilization.

Dr. Nektarios Tavernarakis (Institute of Molecular Biology and Biotechnology, Greece) investigates how autophagy controls neuronal function and dysfunction (Fang et al. 2019; Nikoletopoulou et al. 2017). In his talk, he linked defects in mitophagy to mitochondrial accumulation during aging. He showed that accumulation of damaged mitochondria shortens lifespan in C. elegans, while preventing such accumulation by enhancing mitophagy promotes longevity. Neurons are particularly sensitive to accumulation of mitochondria, and inhibition of mitophagy enhances neurodegeneration, while induction of mitophagy restores associative learning in a worm model of Alzheimer’s disease. Interestingly, mitophagy is also associated with behavioral plasticity under physiological conditions.

Altogether, the results presented in this session highlight the importance of autophagy as a key cellular process controlling physiology and disease, from heart failure to neurodegeneration and aging. Encouraging enough, all the talks touched upon strategies to target autophagy to treat diseases, although the data is limited to animal models and cell lines. It will be interesting to see how these strategies will be translated to human diseases in the future.

Funding

None.

Declarations

Conflict of interest

The author declares no competing interests.