Mitochondria

Mitochondria are specialized structures unique to the cells of animals, plants and fungi. They
serve as batteries, powering various functions of the cell and the organism. Though
mitochondria are an integral part of the cell, evidence shows that they evolved from primitive
bacteria.

Morphology:
The shape of mitochondria varies according to the functional stages of the cell. In
general, these organelles are filamentous or granular. A long mitochondrion may swell at one
end to assume the form of a club or be hollowed out to take the form of a tennis racket. At other
times, mitochondria may become vesicular by the appearance of a central clear zone. The size
of mitochondria is also variable; however, in most cells the width is relatively constant (about
0.5 µm), and the length is variable, reaching a maximum of 7 µm.
They are uniformly distributed throughout the cytoplasm, but there may be exceptions.
For example, in certain muscle cells, mitochondria are grouped like rings or braces around the
I-band of the myofibril, or in sperm they are wrapped tightly around the flagellum.
The number of mitochondria in a cell depends on the type and functional state of the
cell. A normal liver cell contains between 1,000 and 1,600 mitochondria, but this number
diminishes during regeneration and also in cancerous state. The number may be as high as
3,00,000 in some oocytes, and some algal cells may contain only one mitochondrion.

Occurrence
All living organisms are built with one fundamental brick: the cell. In some cases, a
single cell constitutes an entire organism. Cells contain genetic material (DNA and RNA), and
they carry out essential functions, such as metabolism and protein synthesis. Cells are also
capable of self-replicating. However, the level of organization varies within the cells of
different organisms. Based on these differences, organisms are divided into two groups:
eukaryotes and prokaryotes.
Plants, animals and fungi are all eukaryotes and have highly ordered cells. Their genetic
material is packaged into a central nucleus. They also have specialized cellular components
called organelles, each of which executes a specific task. Organelles such as the mitochondria,
the rough endoplasmic reticulum and the golgi serve respectively to generate energy,
synthesize proteins and package proteins for transport to different parts of the cell and beyond.
The nucleus, as well as most eukaryotic organelles, is bound by membranes that regulate the
entry and exit of proteins, enzymes and other cellular material to and from the organelle.
Prokaryotes, on the other hand, are single-celled organisms such as bacteria and
archaea. Prokaryotic cells are less structured than eukaryotic cells. They have no nucleus;
instead their genetic material is free-floating within the cell. They also lack the many
membrane-bound organelles found in eukaryotic cells. Thus, prokaryotes have no
mitochondria.
Structure
In a 1981 review of the history of mitochondria in the Journal of Cell Biology, authors
Lars Ernster and Gottfried Schatz note that the first true observation of mitochondria was by
Richard Altmann in 1890. While Altmann called them “bioblasts,” their current, visually
descriptive name was given by Carl Benda in 1898, based on his observations of developing
sperm. “Mitochondria” derives from two Greek words: “mitos” meaning thread, and
“chondros” meaning granule.
Individual mitochondria are capsule shaped, with an outer membrane and an undulating
inner membrane, which resembles protruding fingers. These membranous pleats are called
cristae and serve to increase the overall surface area of the membrane. When compared to
cristae, the outer membrane is more porous and is less selective about which materials it lets
in. The matrix is the central portion of the organelle and is surrounded by cristae. It contains
enzymes and DNA. Mitochondria are unlike most organelles (with an exception of plant
chloroplasts) in that they have their own set of DNA and genes that encode proteins.
Plant mitochondria were first observed by Friedrich Meves in 1904, as mentioned by
Ernster and Schatz (Journal of Cell Biology, 1981). While plant and animal mitochondria do
not differ in their basic structure, Dan Sloan, an assistant professor at the University of
Colorado said, their genomes are quite different. They vary in size and structure.
According to Sloan, the genomes of most flowering plants are about 100,000 base pairs in size,
and can be as large as 10 million base pairs. In contrast, mammalian genomes are about 15,000
to 16,000 base pairs in size. Moreover, while the animal mitochondrial genome has a simple
circular configuration, Sloan said that the plant mitochondrial genome, though depicted as
circular, could take on alternate forms. “Their actual structure in vivo [within the plant] is not
well understood. They might be complex branched molecules,” he said.
Each mitochondrion is bounded by two highly specialized membranes. An outer limiting
membrane, about 6 nm thick, surrounding the organelle. Within this membrane, separated from
it by a space of about 6 to 8 nm, is an inner membrane. The inner membrane projects into the
mitochondrial cavity and forms complex infoldings called mitochondrial crests.
This inner membrane divides the inner mitochondrial space into two chambers or
compartments:
(a) The outer chamber contained between the two membranes and in the core of crests and
(b) The inner chamber, In some cases, the matrix contains a finely filamentous material, or
highly dense small granules (Fig. 3.13). These granules contain phospholipids, which give
them an affinity for calcium. Within the matrix small ribosomes (55S), circular DNA, some
soluble proteins and lipids are present.

Cristae:
In general, the mitochondrial crests are incomplete septa or ridges that do not interrupt
the continuity of the inner chamber; thus the matrix is continuous within the mitochondrion.
The cristae of animal cells are usually lamellar or plate-like, but in many protozoa and in steroid
synthesizing cells including the adrenal cortex and corpus luteum, they occur as regularly
packed tubules. The cristae greatly increase the area of inner membrane.
F1 particles:
If a mitochondrion is allowed to swell and break in a hypotonic solution and is then
immersed in phospho-tungstate, the inner membrane in the crest appears covered by particles
of 8.5 nm. These particles have a stem linking each with the membrane (Fig. 3.14). These
particles are called ‘elementary’ or ‘F1‘ or F0-F1‘ particles and are regularly spaced at intervals
of 10 nm on the inner surface of these membranes.

The presence of such F1 particles on the matrix side (M) confers to the inner mitochondrial
membrane, a characteristic asymmetry that is of fundamental importance to its function i.e.,
formation of ATP.

Origins of mitochondria: The Endosymbiont Theory

In her 1967 paper, “On the Origins of Mitosing Cells,” published in the Journal of
Theoretical Biology, scientist Lynn Margulis proposed a theory to explain how eukaryotic cells
along with their organelles were formed. She suggested that mitochondria and plant
chloroplasts were once free-living prokaryotic cells that were swallowed up by a primitive
eukaryotic host cell.
Margulis’ hypothesis is now known as the “endosymbiont theory.” Dennis Searcy, emeritus
professor at University of Massachusetts Amherst, explained it as follows: “Two cells began
to live together, exchanging some sort of substrate or metabolite [product of metabolism, like
ATP]. The association became mandatory, so that now, the host cell cannot live separately.”
Even at the time that Margulis proposed it, versions of the endosymbiont theory were already
in existence, some dating back to 1910 and 1915. “Although these ideas are not new, in this
paper they have been synthesized in such a way as to be consistent with recent data on the
biochemistry and cytology of subcellular organelles,” she wrote in her paper. According to a
2012 article on mitochondrial evolution by Michael Gray in the journal Cold Spring Harbor
Perspectives in Biology, Margulis based her hypothesis on two key pieces of evidence. First,
mitochondria have their own DNA. Second, the organelles are capable of translating the
messages encoded in their genes to proteins, without using any of the resources of the
eukaryotic cell.
Genome sequencing and analyses of mitochondrial DNA have established that
Margulis was correct about the origins of mitochondria. The lineage of the organelle has been
traced back to a primitive bacterial ancestor known as alphaproteobacteria (α-proteobacteria).
Despite the confirmation of the mitochondria’s bacterial heritage, the endosymbiont
theory continues to be researched. “One of the biggest questions right now is, 'Who is the host
cell?'” Sloan told LiveScience. As Gray noted in his article, the questions that linger are
whether mitochondria originated after the eukaryotic cell arose (as hypothesized in the
endosymbiont theory) or whether mitochondria and host cell emerged together, at the same
time.

Ultrastructure of Mitochondria:
In 1953, Palade and Sjostrand independently described the ultrastructure of
mitochondria. Mitochondria are bounded by an envelope consisting of two concentric
membranes, the outer and inner membranes. The space between the two membranes is called
inter-membrane space. A number of invaginations occur in the inner membrane; they are called
cristae (Fig. 2.21). The space on the interior of the inner membrane is called matrix.
Outer Membrane:
The outer mitochondrial membrane has high permeability to molecules such as sugars,
salts, coenzymes and nucleotides etc. It has many similarities with the ER but differs from it in
some respects, e.g., mono-amine-oxidase is present in the mitochondrial outer membrane but
not in ER. On the other hand, the enzyme glucose-6-phosphatase is absent from the
mitochondrial outer membrane but is present in ER. The mitochondrial outer membrane
contains a number of enzymes and proteins (Table 2.6).

Inter-Membrane Space:
The inter-membrane space is divided into two regions:
(1) Peripheral space and
(2) Intracristal space (Fig. 2.21).

Large flattened cristae are connected to the inner membrane by small tubes called peduculi
cristae which are few nanometers in diameter. The inter-membrane space has several enzymes
of which “adenylate kinase” is the chief one (Table 2.6). This enzyme transfers one phosphate
group from ATP to AMP to produce two molecules of ADP.

Inner Membrane:
The inner mitochondrial membrane invaginates inside the matrix; the invaginations are called
cristae (Fig. 2.21). This membrane has a high ratio of protein to lipid. “Knobs” or “spheres” of
8-9 nm diameter are spaced 10 nm apart on the cristae membranes. These knobs contain F1
proteins and ATPase responsible for phosphorylation. They are joined to the cristae by 3 nm
long stalks called “F0“. The F0-F1 ATPase complex” is called ATP synthase. The inner
membrane contains large number of proteins which are involved in electron transfer
(respiratory chain) and oxidative phosphorylation (Table 2.6). The respiratory chain is located
within the inner membrane, and consists of pyridine nucleotides, within the inner membrane,
and consists of pyridine nucleotides, flavoproteins, cytochromes, iron-sulphur proteins and
quinones.
Besides its role in electron transfer, and phosphorylation, the inner membrane is also the site
for certain other enzymatic pathways, such as, steroid (hormone) metabolism.
Matrix:
The interior of mitochondrion is called matrix (Fig. 2.21). It has granular appearance in electron
micrographs. Some large granules ranging from 30 nm to several hundred nanometers in
diameter are also present in the matrix. The matrix contains enzymes and factors for Krebs
cycle, pyruvate dehydrogenase and the enzymes involved in β-oxidation of fatty acids. (Table
2.6). However, succinate dehydrogenase is present in the inner membrane instead of matrix;
this enzyme catalyses the direct transfer of electrons from succinate to the electron transfer
chain.
The enzyme pyruvate dehydrogenase converts pyruvate to acetyl-Coenzyme A (acetyl-
CoA) which enters the Krebs cycle. Besides above, matrix also contains DNA, RNA,
ribosomes and proteins involved in protein and nucleic acid syntheses.

Chemical Composition of Mitochondria:

The gross chemical composition of the mitochondria varies in different animal and
plant cells. In general, mitochondria are found to contain 65 to 70% proteins, 25 to 30% lipids,
0.5% RNA and small amount of DNA. The lipid content’ of mitochondria are composed of
90% phospholipids, 5% or less cholesterol and 5% free fatty acids and triglycerides. The inner
membrane is rich in the phospholipid, called cardiolipin that makes the membrane impermeable
to various ions and small molecules. The enzyme composition of mitochondrial compartments
and membranes are shown in Table 3.2:
Functions of Mitochondria:

a. Mitochondria function as energy-transducing organelle into which the major degradation

products of cell metabolism penetrate and are converted into chemical energy (ATP) that is
used in various activities of the cell. The process of energy transformation that occur in
mitochondria are based on three coordinated steps:
(i) Krebs cycle, carried out by a series of soluble enzymes present in the matrix, which produces
CO2 by decarboxylation and removes electrons from the metabolites.
(ii) The respiratory chain or electron transport system, which captures the pairs of electrons
and transfers them through a series of electron carriers, which finally leads by combination
with activated oxygen to the formation of H2O.
(iii) A phosphorylating system, tightly coupled in the respiratory chain, which at three points
gives rise to ATP molecules.

b. In the mitochondria of all cells, the outer membrane enzymes mediate the movement of free
fatty acids into the mitochondrial matrix. In the matrix, each fatty acid molecule is broken down
completely by a cycle of reactions, called P-oxidation that trims two carbons from its carboxyl
end, generating one molecule of acetyl-CoA in each turn of cycle. This acetyl-CoA is fed into
Krebs cycle for further oxidation.

c. Besides the ATP production, mitochondria perform certain biosynthetic or anabolic

functions. It contains DNA and the machinery needed for protein synthesis. Therefore, it can
make different proteins of its own. These proteins include subunits of ATP synthase, portions
of the reductase and three of the seven subunits in cytochrome oxidase. The synthesis of haeme
(needed for myoglobin, haemoglobin) begins with a mitochondrial reaction catalyzed by the
enzyme delta or d-aminolevulinic acid synthetase. Likewise, some early steps in the conversion
of cholesterol to steroid hormones in the adrenal cortex are also catalyzed by mitochondrial
enzymes.

d. Sometimes the mitochondria assume storage functions, e.g., the mitochondria of ovum store
large amounts of yolk proteins and transform them into yolk platelets.

e. A secondary function of mitochondria is to synthesize proteins for their own use. They work
independently, and execute the transcription of DNA to RNA, and translation of RNA to amino
acids (the building blocks of protein), without using any components of the cell.