Microbiology and Immunology

Mitochondria and cellular energy WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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bodies. He and Köhler produced a hybrid myeloma called

hybridoma in 1974. This cell had the capacity to produce anti-

bodies but kept growing like the cancerous cell from which it

had originated. The production of monoclonal antibodies from

these cells was one of the most relevant conclusions from

Milstein and his colleague’s research. The Milstein-Köhler

paper was first published in 1975 and indicated the possibility

of using monoclonal antibodies for testing antigens. The two

scientists predicted that since it was possible to hybridize anti-

body-producing cells from different origins, such cells could

be produced in massive cultures. They were, and the technique

consisted of a fusion of antibodies with cells of the myeloma

to produce cells that could perpetuate themselves, generating

uniform and pure antibodies.

In 1983, Milstein assumed leadership of the Protein and

Nucleic Acid Chemistry Division at the Medical Research

Council’s laboratory. In 1984, he shared the Nobel Prize with

Köhler and Jerne for developing the technique that had revo-

lutionized many diagnostic procedures by producing excep-

tionally pure antibodies. Upon receiving the prize, Milstein

heralded the beginning of what he called “a new era of

immunobiochemistry,” which included production of mole-

cules based on antibodies. He stated that his method was a by-

product of basic research and a clear example of how an

investment in research that was not initially considered com-

mercially viable had “an enormous practical impact.” By

1984, a thriving business was being done with monoclonal

antibodies for diagnosis, and works on vaccines and cancer

based on Milstein’s breakthrough research were being rapidly

developed.

In the early 1980s, Milstein received a number of other

scientific awards, including the Wolf Prize in Medicine from

the Karl Wolf Foundation of Israel in 1980, the Royal Medal

from the Royal Society of London in 1982, and the Dale

Medal from the Society for Endocrinology in London in 1984.

He was a member of numerous international scientific organ-

izations, among them the U.S. National Academy of Sciences

and the Royal College of Physicians in London.

See alsoAntibody and antigen; Antibody formation and kinet-

ics; Antibody, monoclonal; Antibody-antigen, biochemical

and molecular reactions

MINIMUMINHIBITORYCONCENTRATION

(MIC)•seeANTIBIOTICS

MMitochondria and cellular energyITOCHONDRIA AND CELLULAR ENERGY

Mitochondria are cellular organelles found in the cytoplasmin

round and elongated shapes, that produce adenosine tri-phos-

phate (ATP) near intra-cellular sites where energy is needed.

Shape, amount, and intra-cellular position of mitochondria are

not fixed, and their movements inside cells are influenced by

the cytoskeleton, usually in close relationship with the ener-

getic demands of each cell type. For instance, cells that have a

high consumption of energy, such as muscular, neural, retinal,

and gonadic cells present much greater amounts of mitochon-

dria than those with a lower energetic demand, such as fibrob-

lasts and lymphocytes. Their position in cells also varies, with

larger concentrations of mitochondria near the intra-cellular

areas of higher energy consumption. In cells of the ciliated

epithelium for instance, a greater number of mitochondria is

found next to the cilia, whereas in spermatozoids they are

found in greater amounts next to the initial portion of the fla-

gellum, where the flagellar movement starts.

Mitochondria have their own DNA, RNA(rRNA, mRNA

and tRNA) and ribosomes, and are able to synthesize proteins

independently from the cell nucleusand the cytoplasm. The

internal mitochondrial membrane contains more than 60 pro-

teins. Some of these are enzymesand other proteins that con-

stitute the electron-transporting chain; others constitute the

elementary corpuscle rich in ATP-synthetase, the enzyme that

promotes the coupling of electron transport to the synthesis of

ATP; and finally, the enzymes involved in the active transport

of substances through the internal membrane.

The main ultimate result of respirationis the generation

of cellular energy through oxidative phosphorilation, i.e., ATP

formation through the transfer of electrons from nutrient mol-

ecules to molecular oxygen. Prokaryotes, such as bacteria, do

not contain mitochondria, and the flow of electrons and the

oxidative phosphorilation process are associated to the inter-

nal membrane of these unicellular organisms. In eukaryotic

César Milstein

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