Michael Vivian Berridge (born 1946) is a New Zealand cell biologist. Since 1976, he has led the cancer cell and molecular biology research group at the Malaghan Institute of Medical Research. He is also a professor at Victoria University of Wellington and a Distinguished Research Fellow at the Malaghan Institute of Medical Research. He is best known for elucidating cellular mechanisms of reduction of tetrazolium dyes that are widely used in biology, and for the discovery of mitochondrial genome transfer from healthy cells to mitochondrial DNA-deficient cancer cells.
Berridge was born in Auckland in 1946 and was brought up in Northland, Naumai and Dargaville. He did an undergraduate in Chemistry at the University of Auckland and conducted his honours project in cell biology. [1] Following this, he continued to study at the University of Auckland, completing an MSc (Hons) in 1969 and a PhD [2] in cell biology in 1971 working with a group of plant growth hormones called cytokines. These theses investigated how kinetin interacts with protein synthesis in plants. [3]
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In 1973, Berridge undertook a postdoctoral position at Purdue University in developmental molecular biology. working under Professor Arthur Aronson. There, he investigated how mRNA formed from heterogeneous nuclear RNA, including exploration of enzymes involved in RNA processing. He then undertook a staff scientist position at the National Institute for Medical Research, Mill Hill London, UK, working under Dr Jamshed Tata in Developmental Biology.
In 1976, he returned to New Zealand and established the Cancer Cell & Molecular Biology Research Group as one of the founding researchers of the Wellington Cancer & Medical Research Institute, later renamed the Malaghan Institute of Medical Research. [4] Here, he first investigated blood cell development, with a focus on determinants of stem cells differentiation. His research group then collaborated with Dr Fu-Keun Lin at Amgen to characterise the cellular receptor of the red cell hormone, erythropoietin, and its ability to stimulate platelet production.
Having found that cytokines and hormones change the way in which glucose is taken up by cells, Berridge shifted his research focus to glucose metabolism. Research from 2009 to 2015, in collaboration Professor Jiri Neuzil (Griffith University, QLD, Australia and BIOCEV, Prague, and Dr Lanfeng Dong (Griffith University, QLD) used mitochondrial DNA polymorphisms to unequivocally show mitochondrial genome transfer from healthy cells to cancer cells lacking mitochondrial DNA, and that this occurred by intercellular mitochondrial transfer.
As a result he shifted his research focus to mitochondrial cancer biology. Using genetic knock-out mouse models, his lab group currently investigates how proteins encoded in nuclear DNA contribute to the formation of mitochondrial respiratory complexes and the role of these complexes in tumour metastasis. He is also applying this knowledge to develop an early detection assay for mitochondrial damage in neurodegenerative diseases.
Berridge has published popular science books including The Edge of Life in 2015, and Sugar, Rum and Tobacco: Taxes and Public Health in New Zealand with Lisa Marriott in 2017.
In 2003, Berridge received a James Cook Research Fellowship [5] in health sciences from the Royal Society Te Apārangi.
He was awarded the Health Research Council of New Zealand Liley Medal [6] in 2016 for an outstanding contribution to health and medical sciences in the field of cellular metabolism. The same year he was a semi-finalist in the KiwiBank New Zealander of the Year Award.s [7]
In 2021 he was awarded the Shorland Medal [8] by the New Zealand Association of Scientists in recognition of major and continued contribution to basic or applied research that has added significantly to scientific understanding or resulted in significant benefits to society.
In December 2021, Berridge was awarded a higher Doctorate of Science by Victoria University of Wellington Council, based on a body of published work conducted in close association with the University from 1976-2020.
Adenosine triphosphate (ATP) is a nucleotide that provides energy to drive and support many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of life, it is often referred to as the "molecular unit of currency" of intracellular energy transfer.
Cell biology is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and functioning of organisms. Cell biology is the study of the structural and functional units of cells. Cell biology encompasses both prokaryotic and eukaryotic cells and has many subtopics which may include the study of cell metabolism, cell communication, cell cycle, biochemistry, and cell composition. The study of cells is performed using several microscopy techniques, cell culture, and cell fractionation. These have allowed for and are currently being used for discoveries and research pertaining to how cells function, ultimately giving insight into understanding larger organisms. Knowing the components of cells and how cells work is fundamental to all biological sciences while also being essential for research in biomedical fields such as cancer, and other diseases. Research in cell biology is interconnected to other fields such as genetics, molecular genetics, molecular biology, medical microbiology, immunology, and cytochemistry.
A mitochondrion is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used throughout the cell as a source of chemical energy. They were discovered by Albert von Kölliker in 1857 in the voluntary muscles of insects. The term mitochondrion was coined by Carl Benda in 1898. The mitochondrion is popularly nicknamed the "powerhouse of the cell", a phrase coined by Philip Siekevitz in a 1957 article of the same name.
The northern blot, or RNA blot, is a technique used in molecular biology research to study gene expression by detection of RNA in a sample.
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other, nicotinamide. NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD+ and NADH (H for hydrogen), respectively.
In chemistry and biology, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O2), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (O2H), superoxide (O2-), hydroxyl radical (OH.), and singlet oxygen. ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations.
The MTT assay is a colorimetric assay for assessing cell metabolic activity. NAD(P)H-dependent cellular oxidoreductase enzymes may, under defined conditions, reflect the number of viable cells present. These enzymes are capable of reducing the tetrazolium dye MTT, which is chemically 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, to its insoluble formazan, which has a purple color. Other closely related tetrazolium dyes including XTT, MTS and the WSTs, are used in conjunction with the intermediate electron acceptor, 1-methoxy phenazine methosulfate (PMS). With WST-1, which is cell-impermeable, reduction occurs outside the cell via plasma membrane electron transport. However, this traditionally assumed explanation is currently contended as proof has also been found of MTT reduction to formazan in lipidic cellular structures without apparent involvement of oxidoreductases.
Human mitochondrial genetics is the study of the genetics of human mitochondrial DNA. The human mitochondrial genome is the entirety of hereditary information contained in human mitochondria. Mitochondria are small structures in cells that generate energy for the cell to use, and are hence referred to as the "powerhouses" of the cell.
The study of the tumor metabolism, also known as tumor metabolome describes the different characteristic metabolic changes in tumor cells. The characteristic attributes of the tumor metabolome are high glycolytic enzyme activities, the expression of the pyruvate kinase isoenzyme type M2, increased channeling of glucose carbons into synthetic processes, such as nucleic acid, amino acid and phospholipid synthesis, a high rate of pyrimidine and purine de novo synthesis, a low ratio of Adenosine triphosphate and Guanosine triphosphate to Cytidine triphosphate and Uridine triphosphate, low Adenosine monophosphate levels, high glutaminolytic capacities, release of immunosuppressive substances and dependency on methionine.
The Warburg hypothesis, sometimes known as the Warburg theory of cancer, postulates that the driver of tumorigenesis is an insufficient cellular respiration caused by insult to mitochondria. The term Warburg effect in oncology describes the observation that cancer cells, and many cells grown in vitro, exhibit glucose fermentation even when enough oxygen is present to properly respire. In other words, instead of fully respiring in the presence of adequate oxygen, cancer cells ferment. The Warburg hypothesis was that the Warburg effect was the root cause of cancer. The current popular opinion is that cancer cells ferment glucose while keeping up the same level of respiration that was present before the process of carcinogenesis, and thus the Warburg effect would be defined as the observation that cancer cells exhibit glycolysis with lactate production and mitochondrial respiration even in the presence of oxygen.
The p53 upregulated modulator of apoptosis (PUMA) also known as Bcl-2-binding component 3 (BBC3), is a pro-apoptotic protein, member of the Bcl-2 protein family. In humans, the Bcl-2-binding component 3 protein is encoded by the BBC3 gene. The expression of PUMA is regulated by the tumor suppressor p53. PUMA is involved in p53-dependent and -independent apoptosis induced by a variety of signals, and is regulated by transcription factors, not by post-translational modifications. After activation, PUMA interacts with antiapoptotic Bcl-2 family members, thus freeing Bax and/or Bak which are then able to signal apoptosis to the mitochondria. Following mitochondrial dysfunction, the caspase cascade is activated ultimately leading to cell death.
Fas-activated serine/threonine kinase is an enzyme that in humans is encoded by the FASTK gene.
Sirtuin 4, also known as SIRT4, is a mitochondrial protein which in humans is encoded by the SIRT4 gene. SIRT4 is member of the mammalian sirtuin family of proteins, which are homologs to the yeast Sir2 protein. SIRT4 exhibits NAD+-dependent deacetylase activity.
Hexokinase 2 also known as HK2 is an enzyme which in humans is encoded by the HK2 gene on chromosome 2. Hexokinases phosphorylate glucose to produce glucose-6-phosphate (G6P), the first step in most glucose metabolism pathways. This gene encodes hexokinase 2, the predominant form found in skeletal muscle. It localizes to the outer membrane of mitochondria. Expression of this gene is insulin-responsive, and studies in rat suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells. [provided by RefSeq, Apr 2009]
Mitochondrial carrier homolog 2 also known as MTCH2 is a protein which in humans is encoded by the MTCH2 gene.
In molecular biology mir-126 is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several pre- and post-transcription mechanisms.
The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. When the cell is ready to divide, pRb is phosphorylated, inactivating it, and the cell cycle is allowed to progress. It is also a recruiter of several chromatin remodeling enzymes such as methylases and acetylases.
The TP53-inducible glycolysis and apoptosis regulator (TIGAR) also known as fructose-2,6-bisphosphatase TIGAR is an enzyme that in humans is encoded by the C12orf5 gene.
ADP/ATP translocase 2 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome.
Horizontal transfer of mitochondria is the movement of whole mitochondria and mitochondrial DNA between cells. Mitochondria from donor cells are transported and incorporated into the endogenous mitochondrial network of recipient cells contributing to changes in the bioenergetics profile and in other functional properties of recipient cells. Horizontal cell-to-cell transfer of mitochondria and mitochondrial genome can occur among mammalian cells in vitro and in vivo. Mitochondrial transfer supports the exogenous replacement of damaged mitochondria, thereby rescuing mitochondrial defects. Stem cells, immortalized cells or primary cells are usually used as mitochondrial donors in most studies. These cells may transfer mitochondria to surrounding cells in their niche, thus affecting cell differentiation, proliferation, tissue homeostasis, development and ageing.