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The Nature of Living Things

Mitochondria can undergo fusion and fission; dysfunction in these processes can

lead to debilitating disease. ⁴ Neurons seem to be particularly susceptible to mitochon-

drial dysfunction. Fusion is one way to rescue mitochondrial material that has lost

function, and fission followed by elimination of the fragments is a way to eliminate

irreparably damaged mitochondria. ⁵

Observational Overview

The optical microscope can resolve objects down to a few hundred nanometres in

size. ⁶ This is sufficient for revealing the existence of individual cells (Hooke 1665)

and some of the larger organelles (subcellular organs) present in eukaryotes. The con-

trast of most of this internal structure is low, however, and stains must be applied in

order to clearly reveal them. Thus, the nucleus, chromosomes, mitochondria, chloro-

plasts, and so on can be discerned, even though their internal structure cannot. The

electron microscope, capable of resolving structures down to subnanometre reso-

lution, has vastly increased our knowledge of the cell, although it must always be

borne in mind that the price of achieving this resolution is that the cell has to be

killed, sectioned, dehydrated or frozen, and stained or fixed—procedures that are

likely to alter many of the structures from their living state. ⁷ Mainly through elec-

tron microscopy, a large number of intracellular structures, such as microfilaments,

microtubules, endoplasmic reticulum, Golgi bodies, lysosomes, peroxysomes, and

so on acquired something apparently more substantial than their previous somewhat

shadowy existence.

If cells are mechanically homogenized, different fractions can be separated in the

centrifuge: lipid membrane fragments, nucleic acids, proteins, polysaccharides, and

a clear, mobile aqueous supernatant containing small ions and osmolytes. It should

not be supposed that this supernatant is representative of the cytosol, the term applied

to the medium surrounding the subcellular structures; centrifugation of intact cells

(the experiments of Kempner and Miller) removes practically all macromolecules

along with the lipid-based structures. That experiment was done relatively late in

the development of biochemistry, after the misconception that the cytosol was filled

4 For example, Meyer et al. (2018).

5 Chan (2006) and Westermann (2010) are useful reviews.

6 According to Abbe’s law, the resolutionDelta x equals lamda divided by 2 left parenthesis normal upper N period normal upper A period right parenthesis/\x = λ/2(N.A.), wherelamdaλ is the wavelength of the illu-

minating light and N.A. is the numerical aperture of the microscope condenser. This barrier has now

been broken by some remarkable new techniques developed by S. W. Hell, notably stimulated emis-

sion depletion (STED) and ground state depletion (GSD) microscopies, based on reversible saturated

optical fluorescence transitions (RESOLFT) between two states of a fluorescent marker, typically a

dye introduced into the living cell. The resolution is approximately given byDelta x Subscript normal upper A normal b normal b normal e Baseline divided by StartRoot 1 plus upper I divided by upper I Subscript normal s normal a normal t Baseline EndRoot/\xAbbe/^√1 + I/Isat,

whereupper II is the actual illuminating irradiance andupper I Subscript normal s normal a normal tIsat is the irradiance needed to saturate the transi-

tion.

7 See Hillman (1991) for an extended discussion.