December 23, 2024
Autophagy unveiled: The Dagdas Group is shining a light on cellular recycling
Autophagy is like a cell’s version of housekeeping, tidying up old or damaged components to keep the cell running smoothly. Just as cleaning up a cluttered space prevents chaos, autophagy helps cells to avoid harmful buildups and stay healthy. Through autophagy, old or damaged components such as proteins and organelles are broken down into basic molecules that can be reused, producing energy as a byproduct. When autophagy is disrupted, cells can be severely damaged or die, which may result in diseases such as cancer or neurodegenerative disorders.
Autophagy is highly regulated, with selective autophagy functioning as a cellular quality control mechanism against specific damaged or unwanted structures: Selective autophagy receptors (SARs) identify pathogens, misfolded proteins or damaged organelles, and mark them for degradation, ensuring an efficient response to the most threatening cellular problems. While selective autophagy has been studied in detail in animals, our understanding of how this process works in plants is severely limited.
Yasin Dagdas joined GMI in 2017 as a Junior Group Leader and quickly assembled a team of talented researchers to study selective autophagy in plants. Over the past seven years, Dagdas and his group have made transformative discoveries in the field of plant autophagy, such as identifying the highly conserved C53 protein as a key mediator or endoplasmic reticulum recycling and uncovering how autophagosomes mature and reach their final destination in plant cells. In the last months, four new preprints from the Dagdas group have described new essential features of selective autophagy:
Revealing a plant-specific selective autophagy mechanism
Identifying plant SARs can help us better understand how selective autophagy works in plant cells. While some plant SARs are homologous to their animal counterparts and can be easily identified, other SARs differ significantly between animals and plants, making it difficult to identify them and understand their evolution.
A team including PhD students Víctor Sánchez de Medina Hernández and Marintia Mayola Nava García developed a system to identify new lineage-specific SARs in plants. By studying proteins interacting with a marker for degradation, called ATG8, across five different species of the green lineage, the researchers identified a series of highly conserved SARs. One of these highly conserved SARs, CESAR, plays a crucial role in protein quality control, as it facilitates the degradation of damaged proteins in stress conditions. The research suggests that enhancing CESAR-mediated degradation of damaged proteins could improve plant resilience against harsh environments, with potential applications in agriculture.
Original publication:
Cross-species interactome analysis uncovers a conserved selective autophagy mechanism for protein quality control in plants. De Medina Hernandez VS, Nava Garcia MM, … Dagdas Y (2024) bioRxiv:2024.09.08.611708.
Electrostatic changes enable protein diversification
Cellular processes and trafficking pathways such as autophagy were already present in the common ancestor of eukaryotes; and have further refined during millions of years of evolution. New proteins governing these pathways can evolve from pre-existing ones through duplication and specialization. However, the evolution of many proteins is constrained because they are part of multimeric complexes formed by different interacting proteins. Scientists have long wondered how proteins inserted in complexes that perform essential functions in the cell can change and evolve novel functions without compromising their ancestral role.
To answer this question, Postdoctoral Fellow Juan Carlos De la Concepcion and colleagues studied an essential trafficking pathway called exocytosis, which regulates the secretion of different components to the extracellular space. This process depends on the exocyst, a complex of eight different proteins. The team studied the evolutionary trajectory of one of the proteins in the exocyst, Exo70, and discovered that small changes in the protein’s N-terminal region reduced its electrostatic affinity to other subunits of the exocyst complex. These changes allow Exo70 to escape the exocyst complex and gain novel functions and interactions. The team’s research revealed a simple yet effective mechanism for functional diversification that could help explain unexpected instances of protein evolution.
Original publication:
Electrostatic changes enabled the diversification of an exocyst subunit via protein complex escape. De la Concepcion JC, Duverge H, … Dagdas Y (2024) bioRxiv:2024.08.26.609756.
Moonlighting metabolic enzymes protect plant cells against viral damage
After infecting a cell, viruses hijack various cellular structures and use them to replicate. Selective autophagy is one defense mechanism to eliminate infected organelles. However, how infected organelles are identified in the first place was unknown. The Dagdas group explored this question by studying how Arabidopsis thaliana cells respond to three viral infections targeting different cellular compartments.
Led by Postdoctoral Fellow Marion Clavel, now group leader at the Max Planck Institute of Molecular Plant Physiology, the team described a new autophagy pathway in which two metabolic enzymes moonlight as selective autophagy receptors, degrading key executors of cell death and dampening autoimmune responses to give plant cells a chance to recover. The team’s efforts uncovered an organelle health monitoring system that is likely relevant in antiviral response in other species.
Original publication:
Metabolic enzymes moonlight as selective autophagy receptors to protect plants against viral-induced cellular damage. Clavel M, Bianchi A, Kobylinska R, et al. (2024) bioRxiv:2024.05.06.590709.
Balancing the pressure
A unique feature of plant cells is the vacuole, a membrane-enclosed, water-filled compartment that occupies a large part of the plant cell and is essential to the cell’s integrity. However, damage to the plant’s cell wall can alter the pressure balance between the inside and outside of the vacuole’s membrane, risking vacuole rupture and cell death.
The Dagdas group investigated how plant cells use selective autophagy to tackle cell wall disruptions and discovered a mechanism that protects the integrity of the vacuole. Upon recognizing cell wall damage, ATG8 is conjugated to the vacuole membrane. This conjugation potentially isolates the damaged parts of the vacuole to preserve vacuolar integrity. Identifying this system opens the door for further studying the link between the stability of the cell wall and the vacuole and its impact on plant cell survival.
Original publication:
ATG8ylation of vacuolar membrane protects plants against cell wall damage. Julian J, Gao P, … Dagdas Y (2024) bioRxiv:2024.04.21.590262.
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Read more about the research of the Dagdas lab at the GMI and in our Special Research Program.