Biology of Disease

contains five protein complexes (Table 16.2) that together with cytochrome
c perform the energy transduction reactions with the formation of ATP by
oxidative phosphorylation. The matrix contains enzymes that catabolize fuel
molecules to yield the reduced coenzymes NADH and FADH 2 necessary for
oxidative phosphorylation, and produces small organic molecules that are
the precursors in biosynthetic metabolism. The mitochondria also help in
maintaining the intracellular homeostasis of many metabolites and ions,
including Ca2+ and H+.

MITOCHONDRIAL DISORDERS

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Complex Name Comment

Complex I

Complex II

reduced nicotinamide adenine

dinucleotide (NADH): ubiquinone

reductase

succinate: ubiquinone

oxidoreductase

complexes I and II transfer electrons

from NADH and succinate respectively to

the mobile carrier,ubiquinonewhich then

transfers them to complex III.

Compex III ubiquinone: ferricytochromec

oxidoreductase

complex III then transfers electrons to the

second mobile carrier, cytochromec, which

transfers them to complex IV.

Complex IV cytochromecoxidase complex IV donates electrons, in turn,

to dioxygen.

Complex V ATP synthase synthesizes ATP from ADP and Piwhen

stimulated by H+.

Table 16.2The protein complexes of the inner mitochondrial membrane involved in oxidative phos-
phorylation

Mitochondria are also involved in cellular responses to environmental tox-
ins that can stimulate them to release a potent mixture of enzymes and other
proteins that eventually bring about the death of the cell. This is one form of
apoptosis or cell suicide. These apoptotic mechanisms are, of course, under
strict regulation, but defects in these controls cause some neurodegenerative
and autoimmune diseases and some cancers.

Mitochondria are unusual organelles, in that the matrix also contains
molecules of mitochondrial DNA (mtDNA) containing mitochondrial genes,
in addition to mitochondrial ribosomes and mitochondrial transfer RNA
molecules. Mitochondrial ribosomes differ in size and structure from those
present in the cytosol.

Human mitochondrial DNA is a circular double-stranded molecule of 16 569
base pairs present in multiple copies in each mitochondrion. Human mtDNA
has been completely sequenced and contains only 37 genes (Figure 16.7).
Twenty-eight genes are encoded on one of the strands of the DNA and nine
genes on the other. These genes encode 22 transfer RNAs, the 12S and 16S
mitochondrial ribosomal RNAs, and 13 mitochondrial polypeptides that are
involved in oxidative phosphorylation. Thus, mitochondria have the genetic
information and machinery to synthesize proteins. Mitochondria contain
approximately 1000 different proteins, that is about 3% of all cellular proteins.
It follows that the majority of mitochondrial proteins are encoded by nuclear
genes and are synthesized on ribosomes in the cytosol. These proteins require
transportation across one or both of the mitochondrial membranes to reach
their sites of activity.

Causes of Mitochondrial Disorders

Mitochondrial disorders are a heterogeneous group of disorders resulting
from impairment of the mitochondrial oxidative phosphorylation system.