TokyoTechX: Bio150x Autophagy: Research Behind the 2016 Nobel Prize in Physiology or Medicine

Course Glossary

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• Aberrant protein – an atypical, abnormal form of a protein. Aggregations of aberrant proteins in the brain can cause neurodegenerative diseases, such as Parkinson’s disease.
• Acute pancreatitis – an inflammation of the pancreas that causes abdominal pain.
• Amino Acid – an organic molecule comprising an amino group, a carboxyl group and a variable ‘R’ group. Amino acids can be arranged into chains of various orders to form polypeptides (proteins) that are able to achieve diverse and specific functions within cells.
• Anti-aging – a process that prevents or slows the changes associated with aging in a living cell or organism.
• Antibody – a class of proteins produced by the immune system of animal cells that specifically binds to a foreign, disease-causing molecule, facilitating its destruction by the immune system and the prevention of infection.
• Autophagic body – the single membrane-bound vesicle that is released into the vacuole or lysosome and is derived from the inner membrane of the autophagosome. Upon release into the vacuole, the autophagic body and its contents are degraded by vacuolar/lysosomal enzymes.
• Autophagosome – a double-layer vesicle that forms in the cytoplasm due to the concerted activity of the autophagy-related proteins. The autophagosome is the key functional unit of autophagy, capturing cytoplasmic components and transporting them to the vacuole/lysosome for degradation.
• Autophagy – The controlled degradation of a cell’s own components. Autophagy occurs through the isolation of cytoplasmic material within an autophagosome, which is delivered to the vacuole/lysosome and subsequently degraded.
• Bacteria – a large domain of prokaryotic microorganisms that occur universally throughout the world and in some cases can cause diseases in animals.
• Cancer – a disease that arises from the uncontrolled growth of cells in a multicellular organism.
• Cell – the smallest structural and functional unit of all known organisms. Cells can live individually (unicellular organisms) or in groups (multicellular organisms), and can exhibit a high degree of internal organisation, with compartmentalised organelles that perform specific functions.
• Cell senescence – the process of cell deterioration with age.
• Central dogma – the theory, first raised by Francis Crick, that information flow in a cell is essentially unidirectional, passing from deoxyribonucleic acid (DNA) to ribonucleic acid (RNA) and finally to functional proteins. While this theory explains the majority of information transfer within cells, it is now understood that exceptions to this rule exist.

• Chlorosis – In plants, the insufficient production of chlorophyll.

• Crohn’s disease – a chronic inflammatory condition of the gastrointestinal tract, commonly affecting the end of the small bowel (ileum) and the beginning of the colon.
• Cytoplasm – the contents of a cell, excluding the nucleus. Includes the cytosol, a gel-like substance within the boundaries of the cell, within which a complex mixture of proteins, nucleic acids, metabolites and organelles are suspended.
• Dauer – a specialised form of the larval stage of development observed in nematode worms that is highly resistant to starvation and other types of stress.
• Degradation – the condition or process of breaking down. In the cell, this may be controlled and involves the conversion of complex components into basic units that may be reused in synthesis.
• Deoxyribonucleic acid (DNA) – the fundamental hereditary material of all living organisms. DNA is comprised of individual nucleotides arranged in a specific sequence to direct the synthesis of unique proteins from individual amino acids.
• Diabetes – a disease characterised by a chronically high blood glucose level, usually due to abnormal production of insulin. Left untreated, diabetes can cause a range of serious complications.
• Differentiation – the process whereby a cell changes from one type of cell to another. This process is vital for the formation of specialised tissues and organs in developing organisms.
• Digestive compartment – in a cell, an organelle specialised to carry out degradation. The lysosome of animal cells and vacuole of yeast cells are examples of digestive compartments.
• Electron Microscopy (EM) – a type of microscope that uses a beam of electrons to capture images of a specimen. It has higher magnification and greater resolving power than light microscopy, but is labour-intensive and cannot be used to observe living cells.
• Embryogenesis – the process of formation and development of an embryo.
• Endoplasmic reticulum (ER) – a system of membranous and flattened sacs found near the nucleus in the cytoplasm of eukaryotes. The ER is involved in protein synthesis and trafficking, as well as lipid metabolism and cell signalling.
• Endosome – an intracellular membranous vesicle that is involved in the transport of proteins and lipids between the Golgi apparatus, plasma membrane and degradative compartment of the cell. Endosomes are the key functional unit of the endocytic transport pathway.
• Enzyme – A macromolecule (almost always a protein) that acts as a catalyst, accelerating the rate of reactions in cells. Enzymes are required to ensure that the many biological processes occurring within cells occur rapidly enough to sustain life.
• Fetus – a developmental stage of unborn offspring during which the features of the offspring are recognizable. There is no specific biological event that determines the point at which an embryo (the developmental stage prior to a fetus) changes to a fetus. In humans, the fetal stage of development is from 9 weeks until birth.
  
• Fruiting body – see social amoeba
• Fusion – In cells, generally refers to the joining of separate membranes to form a larger membranous entity.
• GFP-LC3 – an autophagosome protein LC3 which is fused with green fluorescence protein (GFP) used to observe the formation of autophagosome with a fluorescence microscope.
• Golgi apparatus - a system of concentrically folded membranes found in the cytoplasm of eukaryotic cells. It is primarily involved in the processing, trafficking and secretion of proteins.

• HeLa cell – a human-derived, immortal cell line that is widely used in biological research. HeLa cells were originally isolated from a cancer in a patient called Henrietta Lacks, and grow easily in tissue culture experiments, allowing scientists to investigate biological phenomena in human cells

• Homeostasis – The intricate and actively regulated balance between competing processes, such as synthesis and degradation, that is essential to maintain a dynamic but stable intracellular environment.

• Hypothalamus cells – Neuronal cells of the hypothalamus, a portion of the brain that is involved in hormonal signalling and the control of basal metabolic processes and circadian rhythms.

• Infectious disease – a disease that is transmittable among people or organisms in the environment.
• Intracellular clearance – the clearance of harmful or old material from a cell’s internal environment. Autophagy is a major component of the cell’s clearance machinery.
• Intracellular degradation – Degradation occurring within the cell. Autophagy and the ubiquitin proteasome system are the two main components of intracellular degradation.
• Intracellular space – the space, comprising the cytoplasm and nucleus, within the plasma membrane of a cell.
• Lipid membranes (or lipid bilayer) – A polar membrane made up of two layers of lipid molecules. Lipid membranes serve as the boundaries of cells and organelles, allowing the compartmentalisation of biological material, and also function in intracellular transport, metabolism and signalling.
• Lipid molecule – a biological molecule that insoluble in water and non-polar. Lipids are a broad class of molecules, including fats, phospholipids and sterols. Lipids are essential for cellular life, and are the primary component of membranes as well as functioning in signalling and playing a range of roles in metabolism.
• Liver – An organ in mammals that is involved in the detoxification of blood, production of digestive enzymes, protein synthesis and a range of other processes.
• Lysosome – an organelle containing hydrolytic enzymes that functions as the degradative compartment in animal cells. Degradation of cellular material by autophagy occurs within the lysosome in mammalian cells (or the vacuole in yeast).
• Malignancy – the presence of a malignant tumor, cancer
• Metabolism – a term used to collectively refer to the chemical reactions occurring within a cell that are essential to sustain life.
• Microbial infection - infection caused by a microorganism, such as bacteria.
• Mitochondrion – an organelle involved in the production of energy in the cell, as well as a range of other signalling and metabolic processes.
• Molecule – a chemical entity, comprising two or more stably binding atoms, that is the smallest unit of a compound.

• Neonate – a newborn organism. For humans, this refers to the first month of life following birth.

• Neurodegeneration - degeneration of the nervous system, especially neurons in the brain, which can have serious pathological implications for the patient.
• Non-selective autophagy – also known as bulk autophagy, this form of autophagy involves the apparently random isolation of portions of the cytoplasm for degradation. Bulk autophagy is strongly induced in response to starvation.
• Nucleus – An organelle containing the heritable genetic material (DNA) that serves as the blueprint for the synthesis of all the components that are built by the cell.
• Oocyte – a cell in an ovary that undergoes cell division to form an ovum.
• Organelles – a hallmark of eukaryotic cells, organelles are small, membrane-bound compartments in the cytoplasm. This compartmentalisation allows organelles to have specific internal environments and functions, for example degradation (vacuole/lysosome), energy production (mitochondria) and gene storage and expression (nucleus).

• Organelle homeostasis – The healthy maintenance of the cell’s complement of organelles by carefully balanced synthesis, degradation and quality control. Autophagy plays a part in this process by selectively degrading organelles or parts of organelles that are no longer required or damaged. 

• Parkinson’s disease – a neurodegenerative disease characterized by the gradual decay of most notably the motor system, which causes shaking and difficulty with everyday tasks such as walking and movement.

• pep4Δ – A strain of yeast in which the PEP4 gene has been deleted (removed) from the genome. In this strain, the vacuolar protein degradation enzyme proteinase A is not produced, limiting the ability of the vacuole to break down material delivered by autophagy.
• Peroxisome – a small organelle that is involved in catabolic processes, most notably fatty acid oxidation, as well as the reduction of reactive oxygen species (a subclass of free radicals).
• Poly-Ub protein (polyubiquitinated protein) – a protein to which numerous ubiquitin molecules have been attached. The attachment of ubiquitin is an important protein modification that can indicate that a protein needs to be degraded.
• Protein – a polymer of various amino acids arranged in a specific order. The order of amino acids allows the protein to realise a specific and unique three-dimensional structure that is crucial to its function.

• Protein turnover – the degradation of protein to its constituent amino acids and subsequent reuse by the cell. Protein turnover often refers collectively to the cycling of protein to amino acids and back to protein in the cell, which depends largely upon the activity of autophagy.

• Pupa – A developmental stage observed in some insects where the insect usually becomes inactive, does not feed and develops the structures of the adult organism. The pupal stage follows the larval stage of development.
• Reactive oxygen species – chemically reactive oxygen-containing chemical species that are a by-product of oxygen metabolism. Examples of this subclass of free radicals include peroxides and superoxides. Their reactivity can result in damage to cellular components (oxidative stress) if they are not removed by the cell.
• Ribonucleic acid (RNA) – a type of nucleic acid formed as a polymer (chain) of ribonucleotides. RNA plays many roles in the cell, including transmitting genetic information from DNA in the nucleus to the cytoplasm (mRNA), synthesising proteins (rRNA) and reading the sequence of DNA nucleotides to ensure the correct incorporation of amino acids into proteins (tRNA).
• Salmonella - genus of rod-shaped Gram-negative bacteria that can be a cause of food poisoning.
• Selective autophagy – the targeted degradation of cellular components by autophagy. Selective autophagy depends on the core autophagy proteins and employs the standard autophagy machinery, but requires receptor and adapter proteins to bring specific targets, which can be as large as entire organelles, into contact with the autophagy machinery.

• Sensory neuropathy – disease affecting sensory neurons. Symptoms include numbness, poor coordination and changes in pain perception.

• Sequestration – the capture of cellular components within a vesicle. In the case of autophagy, this refers to the isolation of material within an autophagosome that is achieved by the closure of the isolation membrane.
• Slime mold – see social amoeba
• Social amoeba – Dictyostelium discoideum, a species of amoeba that lives in soil. This amoeba is noteworthy for its intricate lifecycle, comprising a unicellular amoebic form, a multicellular ‘slug’ stage and finally the development of a fruiting body, which is able to shoot spores vast distances in response to stresses. Social amoeba eat bacteria found in the soil.
• Spore – a robust cellular structure that forms part of the life cycle of many unicellular and multicellular organisms. Spores are generally a single, haploid (containing only one copy of the organism’s genome) cell and are able to withstand extreme environmental conditions, allowing the organism to reproduce and disperse in the face of adverse conditions. 
• Starvation – A state of stress in which the metabolic requirements of a cell or organism are not met by the supply of nutrients from the surrounding environment. During starvation, the organism must draw on its own stores of energy and molecules to synthesise molecules, produce energy and survive. Autophagy, which allows the degradation of cell components to individual building blocks that can be recycled in synthesis, is an important cellular response to starvation.

• Streptococcus pyogenes – a type of round bacterium that can cause diseases in humans.

• Tumorigenesis – the production or formation of tumors
• Vacuolar lumen – the interior of the vacuole, that the limits of which are defined by the vacuolar membrane.
• Vacuole – An organelle that contains enzymes required for degradation that also serves as an important storage site within the cell. Vacuoles are found universally in plant and fungal cells and variously in animal, bacterial and protist cells. Vacuoles also play an important role in maintaining the pH, water pressure and structural integrity of cells. 
• Vesicle – a membrane-bound sac in the cytoplasm of a cell. Vesicles are important for the transport of material within and out of the cell. The fundamental structural unit of autophagy, the autophagosome, is one example of a vesicle.
• Yeast - a type of microscopic, single-celled fungus. The representative species, Saccharomyces cerevisiae, has been used by humans for thousands of years for its ability to ferment in baking and alcohol production, and is an important model organism used in biological research.