Lesson mitochondria bombarely_a20180927

Lezione:
I mitocondri
Cosa, perché, come, dove e quando
Lesson:
The mitochondria
What, why, how, where and when
By
Aureliano Bombarely
aureliano.bombarely@unimi.it
GenoBotanyLab@UNIMI

1. What are the mitochondria?
2. Structure of the mitochondria
3. Functions of the mitochondria
3.1. Celular respiration
4. Mitochondria genetic information
5. Origin and evolution of the mitochondria
6. Diseases associated to mitochondria

The mitochondrion (plural mitochondria) is a double-
membrane-bound organelle found in
most eukaryotic organisms.
https://en.wikipedia.org/wiki/Mitochondrion

Cell types
Erythrocytes
(red blood cells)
https://en.wikipedia.org/wiki/Red_blood_cell

Cell types Eukaryotic species
MonocercomonoidesErythrocytes
(red blood cells)
https://en.wikipedia.org/wiki/Red_blood_cell

Eukaryotic life without mitochondria?
Karnkowska, Anna, et al. "A eukaryote without a mitochondrial organelle." Current Biology 26.10 (2016): 1274-1284.

1. Discovered by Richard Altmann in 1890

1. Discovered by Richard Altmann in 1890 (He named them “bioblast”)

1. Discovered by Richard Altmann in 1890 (He named them “bioblast”)
2. Carl Benda named them “MITOCHONDRIA” in 1898
They lie within of a portion of the protoplasmic threads, sometimes
aggregated to particular bodies, and are identical to at least a
portion of the already known cell microsomes, but differ from
Altmann's and Ehrlich's granulations. I would like to suggest
tentatively reserving for them a special status as "mitochondria",
which I will justify in further work
https://en.wikipedia.org/wiki/Carl_Benda

3. David Keilin discovered cytochromes and described respiratory
chain in 1925

3. David Keilin discovered cytochromes and described respiratory
chain in 1925
(The popular term "powerhouse of the cell" was coined by Philip Siekevitz in 1957.)

Mitochondria generate most of the cell's supply
of adenosine triphosphate (ATP), used as a source
of chemical energy.

The structure of the mitochondrion is divided in five
parts:
1. Outer mitochondria membrane.
2. Intermembrane space
3. Inner mitochondria membrane.
4. Cristae space
5. Matrix

parts:
2. Intermembrane space
3. Inner mitochondria membrane.
4. Cristae
5. Matrix
LAMELLAE

parts:

https://en.wikipedia.org/wiki/Phospholipid
parts:
Simple phospholipid bilayer

https://www.nature.com/scitable/topicpage/mitochondria-14053590/
parts:
It encloses the whole mitochondria

parts:
Contains integral proteins structures called porins
outer mitochondria
inner mitochondria

parts:
outer mitochondria
inner mitochondria
Transport by molecular
diffusion

parts:
outer mitochondria
inner mitochondria
Porins allow pass to
molecules under 5KDa
diffusion

parts:
outer mitochondria
inner mitochondria
Passing molecules
ATP, ADP…
Ions
Monosaccharides
…
diffusion

parts:
It also contains other enzymes with multiple functions
E.g.
Monoamine oxigenase
(MAO)
E.g.
Kynurenine
hydroxylase
degradation of
tryptophan
• Breakdown of
monoamines ingested in
food
• Inactivation of monoamine
neurotransmitters

E.g.
Monoamine oxigenase
(MAO)
• Breakdown of
monoamines ingested in
food
• Inactivation of monoamine
neurotransmitters
Too many
Too few
Some human diseases associated to unusual low or high
levels of Monoamine Monoxigenase (MAO):
• Schizophrenia
• Depression
• Attention deficit disorder
• Substance abuse
• Migraines

parts:
2. Intermembrane space.
outer membrane
intermembrane mitochondria space
inner membrane
Same small molecule
composition than the cytosol
Different protein composition
than the cytosol
E.g. cytochrome C

parts:
3. Inner membrane.
It is extensively folder and compartmentalized
outer membrane
inner membrane
(5x more surface)

parts:
3. Inner membrane.
It has invaginations called cristae
cristae
cristae
outer membrane
inner membrane
(5x more surface)

parts:
3. Inner membrane.
Protein-to-lipid ratio is 80:20 (in outer membrane is 50:50)
outer membrane inner membrane

parts:
3. Inner membrane.
It is freely permeable to oxygen, carbon dioxide, and water only
Requirement for the metabolic function

parts:
3. Inner membrane.
It is freely permeable to oxygen, carbon dioxide, and water only
It contains more than 151 different polypeptides
Electronic transport chain
Carnitine transferases
…

parts:
4. Cristae space
It is a fold in the inner membrane of a mitochondrion
cristae
cristae
Increase the surface for chemical reactions
ATP
production

parts:
4. Cristae space
It is a fold in the inner membrane of a mitochondrion
It is the place where it is produced the ATP production
https://www.nature.com/scitable/topicpage/mitochondria-14053590/

parts:
5. Matrix
It is the space within the inner membrane
Matrix

parts:
5. Matrix
The matrix contains: DNA, ribosomes, soluble enzymes,
nucleotide cofactors, small molecules and inorganic ions

parts:
5. Matrix
The matrix contains: DNA, ribosomes, soluble enzymes,
nucleotide cofactors, small molecules and inorganic ions
There are six processes that are produced in the matrix:
Citric acid cycle
Oxidative phosphorilation
Urea cycle
Transamination
Regulation of the metabolic rate
Protein synthesis

The mitochondria have a main function that it is
energy conversion
ATPATP
Glucose
(pyruvate)
+
NADH

The mitochondria have a main function that it is
energy conversion
Glucose
(pyruvate)
+
NADH
ATP
• Pyruvate: Citric acid cycle (TCA or Krebs cycle)
• NADH: Electron transport chain

The mitochondria have several secondary functions
that are:
• Calcium ion storage and signaling
• Signaling (through ROS)
• Regulation of membrane potential
• Apoptosis (programmed cell death)
• Regulation of the cellular metabolism
• Some heme synthesis reaction
• Steroid synthesis
• Hormone signaling

The mitochondria have several secondary functions
that are:
• Calcium ion storage and signaling
• Signaling (through ROS)
• Regulation of membrane potential
• Apoptosis (programmed cell death)
• Regulation of the cellular metabolism
• Some heme synthesis reaction
• Steroid synthesis
• Hormone signaling
CELL TYPE
SPECIFIC

The plant mitochondria have distinct secondary
functions:
• Production of alpha-ketoglutarate or citrate for
ammonia assimilation
• Aminoacid catabolism (valine, leucine,
isoleucine and cysteine)

Celular respiration
Metabolic reactions and processes that take place in
the cells of organisms to convert biochemical
energy from nutrients into adenosine
triphosphate (ATP), and then release waste products
Cytoplasm Mitochondria

Celular respiration

Citric acid cycle (TCA or Krebs cycle)
Series of chemical reactions used by all aerobic organisms to
release stored energy through the oxidation of acetyl-
CoA derived from carbohydrates, fats, and proteins,
into adenosine triphosphate (ATP) and carbon
dioxide.
https://en.wikipedia.org/wiki/Citric_acid_cycle
Eight enzymes
Oxidize acetate from acetyl-CoA into CO2 and water
Reduce three NAD+ into NADH
Reduce one FAD into FADH2
Reduce one GDP + Pi into GTP

dioxide.
Eight enzymes
Oxidize acetate from acetyl-CoA into CO2 and water
Reduce three NAD+ into NADH
Reduce one FAD into FADH2
Reduce one GDP + Pi into GTP
Oxidative
phosphorylation
(to produce ATP)

dioxide.
Acetyl-CoA
+
3 NAD+
+
UQ
+
GDP
+
Pi
+
2 H2O
CoA-SH
+
3 NADH
+
UQH2
+
GTP
+
3H+
+
2 CO2

Oxidative phosphorilation (electron transport-linked
phosphorilation) is the metabolic process in which a series of
electron transfers produce a release of chemical energy that
it is used to produce ATP.
https://en.wikipedia.org/wiki/Oxidative_phosphorylation

https://en.wikipedia.org/wiki/Oxidative_phosphorylation
It is composed by a series of protein and protein complexes with redox
properties. The energy produced is used to pump protons out of the matrix
to the intermembrane space.

In the ﬁnal steps, the protons are pumped back to the matrix by
the ATP synthase producing ATP
https://en.wikipedia.org/wiki/ATP_synthase

The mitochondria genetic information is encoded in the
mitochondria genome
Mitochondrial genomes are often circular DNA molecules with
variable sizes depending of the taxonomic clade.
Animals: ~16 Kb encoding 37 genes
13 for subunits of respiratory complexes I, III, IV and V,
22 for mitochondrial tRNA (20 std Aa + tRNALeu + tRNASer)
2 for rRNA.
Plants: Variable size, from 186 Kb (Marchantia polymorpha) to
2.4 Mb (Cucubita pepo).
May incorporate foreign DNA (nucleus and chloroplast and
horizontal transfer from other organisms)

mitochondria genome
human
mitochondrial
genome
16,569 bp

mitochondria genome
Mitochondrial genomes have different genetic code depending of
the taxonomic group.

mitochondria genome
Mitochondrial genomes are uniparental inhered (e.g. maternal line
in animals)
Very low or inexistent recombination (depends of the taxonomic
group)
Mitochodrial DNA can be repaired by nuclear coding genes. The
enzyme is imported into the mitochodria.

Mitochondrial genomes
de Vries and Archivald, 2018
Mitochondria
Ancestor
Modern
Mitochondria
LAST EUKARYOTIC
ANCESTOR CELL
•All mitochodrial genomes have been shaped by reductive evolution.
•Mitochondria genes encode:
•Information processing machinery (e.g. rRNAs and tRNAs).
•Cell respiratory apparatus (e.g. complex I, ATP synthase..).
•Lineage speciﬁc genes (e.g. horizontal transferred genes in plants)
X Genes Mitochondrial Genes X’ = X - Y + Z Genes
Y >> Z
Y’ transferred to the nucleus

Mitochondrial genomes
Mitochondria
Ancestor
X Genes
?

Last eukaryotic
common ancestorEndosymbiosis
Proteobacterium
Symbiogenesis, or endosymbiotic theory, is an evolutionary
theory of the origin of eukaryotic cells from prokaryotic
organisms.
1. First articulated in 1905 and 1910 by the Russian botanist
Konstantin Mereschkowski.
2. Advanced and substantiated with microbiological evidence
by Lynn Margulis in 1967.
Mitochondria
Ancestor
X Genes

Marechal, 2018
1.First Eukaryotic Common Ancestor (FECA) with endomembrane system.
2.Unknown proteobacterium is engulfed by the FECA cell’s phagosome.
3.Phagosome membrane is not conserved. The mitochondria is formed in the Last Eukaryotic
Common Ancestor (LECA)
4.Unknown cyanobacteria is engulfed by the LECA cell’s phagosome.
5.Phagosome membrane is not conserved. The chloroplast is formed in the First
Archaeplastidia cell
Organelle
origin

Marechal, 2018
1. First Eukaryotic Common Ancestor (FECA) has lineage speciﬁc genes (blue circle).
Along the evolution of these species, it may had multiple Horizontal Gene Transfer (HGT)
events (blue squares).
2. In the symbiotic relationship with the proteobacterium, genes were transferred to the
nucleus (orange squares), leaving some genes in which will become the mitochondria
(orange circles).
3. In the symbiotic relationship with the cianobacteria, genes were transferred to the nucleus
(green squares), leaving some genes in which will become the chloroplast (green circles).
Molecular
integration

Molecular
integration
“Gene loss can provide a selective advantage by conserving an
organism’s limiting resources, provided the gene’s function is
dispensable. Many vital genetic functions are leaky, thereby
unavoidably producing public goods that are available to the entire
community. Such leaky functions are thus dispensable for
individuals, provided they are not lost entirely from the
community.”
Morris et al. 2012

Marechal, 2018
• Mechanisms allowing the transfer of genetic material from the mitochondrion or the
chloroplast to the nucleus are still active.
• Frequency of a gene escape from the chloroplast and mitochondria to the nucleus is at
least of 1 per 5 million cells in Nicotiana tabacum.
Molecular
integration
Nuclear PlasTid (NUPT) DNA
Nuclear MiTochondria (NUMT) DNA

Event
Dating
Primary plastid endosymbiosis
occurred ∼900 Mya (857/1,055 Mya)
and mitochondrial endosymbiosis
occurred ∼1,200 Mya.

6. Diseases associated to mitochondria
Dysfunction of the mitochondria or the mitochondria
components produce a wide range of diseases
depending of the tissue, organ and species
Humans Neurological diseases and
systemic disorders
E.g. Mutations of oxidative phosphorylation enzymes, such
as coenzyme Q10 deﬁciency and Barth syndrome.

Summary and Ideas to take home
• Mitochondrias are organelles that can be found in almost all the
eukaryotic cells
• Its structure can be divided in five parts: Outer membrane,
intermembrane space, inner membrane, cristae and matrix
• Its main function is to produce energy from several substrates (mostly
pyruvate) in form of ATP
• Mitochondrial genomes have an stable size in animals, 16 Kb, but varies
in plants ranging from hundred Kb to several Mb
• Mitochondria are usually uniparentally inherited from the mother
• Mitochondria were originated by the endosymbiosis of a protobacteria
in an Eukaryotic ancestral cell > 1200 MYA

Proposed Group Homework
Orientative Steps:
1. Open an NCBI organelle search page:https://www.ncbi.nlm.nih.gov/genome/
browse#!/organelles/
2. On filter select: Mammals and search “Homo sapiens"
3. Click on the Replicon link
4. Click on the Blast link and run a Blast with the nucleotide database
5. In the results, click “Distance tree of results"
6. Describe your results. Compare the structure across the different taxa.

To know more about the Bombarely lab
https://bombarelylab.com/
@aubombarely

Lesson mitochondria bombarely_a20180927

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