MBS1001
Biomedical challenges
,Case 01
What are mitochondria?
Mitochondrion are membrane-bound organelle found in the cytoplasm of almost
all eukaryotic cells (cells with clearly defined nuclei). Mitochondria are typically round to oval in
shape and range in size from 0.5 to 10 μm. The number of mitochondria per cell varies widely, for
example, in humans, erythrocytes (red blood cells) do not contain any mitochondria,
whereas liver cells and muscle cells may contain hundreds or even thousands.
Functions of mitochondria are:
- Cell respiration:
o Krebs cycle
o Electron transport chain
- The creating of various proteins by the mitochondrial ribosomes
- Lipid synthesis: A set of enzymes that control the synthesis of lecithin and
phosphatidyl-ethanolamine from fatty acids, glycerol, and nitrogen bases are present
in most of the mitochondria.
- Elongation of fatty acids and Lipid signalling in mitochondria: Mammalian
mitochondria have a group of enzymes that carry out the elongation of fatty acids by
adding acetyl-CoA and subsequently reducing the keto acid produced. By this method,
myristate is elongated to palmitate(palmitic acid), palmitate to stearate(Stearic acid),
etc.
- Mitochondria at the crossroads of innate immune signalling and metabolism:
Mitochondria are platforms for MAVS innate immune signalling that modulates
mitochondrial function and integrates immunity with cellular metabolism.
,- Mitochondrial retrograde signalling pathways: Three distinct modes of retrograde signalling
that transform mitochondrial stress into nuclear programs are diagrammed. On the left,
mitochondrial protein folding stress is decoded into nuclear transcription via a lipid
signalling-mediated UPR. In the centre, mitochondrial stress provokes nuclear translocation
of mitochondrial-tethered proteins or peptides that, in turn, initiate transcription of stress
response genes. On the right, mitochondrial stresses, such as an increase in ROS levels, are
translated into epigenetic modifications that facilitate transcriptional up-regulation of stress
response genes.
- Storing calcium for cell signalling activities: The regulation of mitochondrial
Ca2+ transport in physiological and pathological conditions is controlled by channels
and exchangers that are located in the outer and inner mitochondrial membrane.
Whereas the OMM is permeable to solutes and ions, Ca2+ transport across the IMM is
highly regulated. The regulation of mitochondrial Ca2+ transport in physiological and
pathological conditions is controlled by channels and exchangers that are located in
the outer and inner mitochondrial membrane (OMM and IMM, respectively). Whereas
the OMM is permeable to solutes and ions, Ca2+ transport across the IMM is highly
regulated.
- Generation of heat: Mitochondria are thus
microscopic furnaces that inevitably release
, heat as a by-product of these reactions, and this contributes to body warming, especially in
endotherms like birds and mammals. Over the last decade, the idea has emerged that
mitochondria could be warmer than the cytosol, because of their intense energy metabolism.
- Apoptosis-programmed cell death (intrinsic pathway): Bcl-2 family members regulate the
release of proteins from the space between the mitochondrial inner and outer membrane
that, once in the cytosol, activate caspase proteases that dismantle cells and signal efficient
phagocytosis of cell corpses.
- The creation of Fe-S cluster assembly, clusters of iron and silver that make up ribosomes.
What are protein complexes?
- Assemblies of proteins (subunits)
- Often composed of different proteins (hetromultimeric complexes)
- Create larger molecular machineries:
o Channels for transport
o Barrels providing insulated environment for reactions
o Often carry out function that cannot be performed by a single protein
Structure of mitochondria
Special features of mitochondria:
- Mitochondria are unlike other cellular organelles in that they have two
distinct membranes and a unique genome and reproduce by binary fission; these features
indicate that mitochondria share an evolutionary past with prokaryotes.
- In many organisms, the mitochondrial genome is inherited maternally. This is because the
mother’s egg cell donates the majority of cytoplasm to the embryo, and mitochondria
inherited from the father’s sperm are usually destroyed.
- Mitochondria is bound by two specialized membranes, which are the outer and inner
mitochondrial membranes, creating large internal space (matrix) and much narrower space;
the intermembrane space. Both membranes are composed of a lipid bilayer membrane.
Outer membrane contains molecules of transport protein (porin), forming aqueous channels
through the lipid bilayer(permeable to ions/protons in the form of H+ and small molecules up
to 5000 Daltons).
o Inner membrane is folded into cristae, which give increased surface area for electron
transport chain proteins.
o Mitochondria originate from alpha proteobacteria according to the endosymbiotic
theory where multicellular organisms shallowed the bacteria. The bacteria became
evolved to become indispensable of the cell. Therefore the mitochondria has its own
16000 nucleotide long genome. It is only 0,5% of the whole cell genome.
- Double-stranded mtDNA has a circular structure
o Mitochondrial DNA (mtDNA): human mtDNA is a molecule of double-
stranded DNA that encodes 13 structural peptide subunits of the oxidative
phosphorylation system and 24 RNA molecules required for intra-
mitochondrial protein synthesis (22 mitochondrial tRNA and 2 mitochondrial
rRNAs).
-
Biomedical challenges
,Case 01
What are mitochondria?
Mitochondrion are membrane-bound organelle found in the cytoplasm of almost
all eukaryotic cells (cells with clearly defined nuclei). Mitochondria are typically round to oval in
shape and range in size from 0.5 to 10 μm. The number of mitochondria per cell varies widely, for
example, in humans, erythrocytes (red blood cells) do not contain any mitochondria,
whereas liver cells and muscle cells may contain hundreds or even thousands.
Functions of mitochondria are:
- Cell respiration:
o Krebs cycle
o Electron transport chain
- The creating of various proteins by the mitochondrial ribosomes
- Lipid synthesis: A set of enzymes that control the synthesis of lecithin and
phosphatidyl-ethanolamine from fatty acids, glycerol, and nitrogen bases are present
in most of the mitochondria.
- Elongation of fatty acids and Lipid signalling in mitochondria: Mammalian
mitochondria have a group of enzymes that carry out the elongation of fatty acids by
adding acetyl-CoA and subsequently reducing the keto acid produced. By this method,
myristate is elongated to palmitate(palmitic acid), palmitate to stearate(Stearic acid),
etc.
- Mitochondria at the crossroads of innate immune signalling and metabolism:
Mitochondria are platforms for MAVS innate immune signalling that modulates
mitochondrial function and integrates immunity with cellular metabolism.
,- Mitochondrial retrograde signalling pathways: Three distinct modes of retrograde signalling
that transform mitochondrial stress into nuclear programs are diagrammed. On the left,
mitochondrial protein folding stress is decoded into nuclear transcription via a lipid
signalling-mediated UPR. In the centre, mitochondrial stress provokes nuclear translocation
of mitochondrial-tethered proteins or peptides that, in turn, initiate transcription of stress
response genes. On the right, mitochondrial stresses, such as an increase in ROS levels, are
translated into epigenetic modifications that facilitate transcriptional up-regulation of stress
response genes.
- Storing calcium for cell signalling activities: The regulation of mitochondrial
Ca2+ transport in physiological and pathological conditions is controlled by channels
and exchangers that are located in the outer and inner mitochondrial membrane.
Whereas the OMM is permeable to solutes and ions, Ca2+ transport across the IMM is
highly regulated. The regulation of mitochondrial Ca2+ transport in physiological and
pathological conditions is controlled by channels and exchangers that are located in
the outer and inner mitochondrial membrane (OMM and IMM, respectively). Whereas
the OMM is permeable to solutes and ions, Ca2+ transport across the IMM is highly
regulated.
- Generation of heat: Mitochondria are thus
microscopic furnaces that inevitably release
, heat as a by-product of these reactions, and this contributes to body warming, especially in
endotherms like birds and mammals. Over the last decade, the idea has emerged that
mitochondria could be warmer than the cytosol, because of their intense energy metabolism.
- Apoptosis-programmed cell death (intrinsic pathway): Bcl-2 family members regulate the
release of proteins from the space between the mitochondrial inner and outer membrane
that, once in the cytosol, activate caspase proteases that dismantle cells and signal efficient
phagocytosis of cell corpses.
- The creation of Fe-S cluster assembly, clusters of iron and silver that make up ribosomes.
What are protein complexes?
- Assemblies of proteins (subunits)
- Often composed of different proteins (hetromultimeric complexes)
- Create larger molecular machineries:
o Channels for transport
o Barrels providing insulated environment for reactions
o Often carry out function that cannot be performed by a single protein
Structure of mitochondria
Special features of mitochondria:
- Mitochondria are unlike other cellular organelles in that they have two
distinct membranes and a unique genome and reproduce by binary fission; these features
indicate that mitochondria share an evolutionary past with prokaryotes.
- In many organisms, the mitochondrial genome is inherited maternally. This is because the
mother’s egg cell donates the majority of cytoplasm to the embryo, and mitochondria
inherited from the father’s sperm are usually destroyed.
- Mitochondria is bound by two specialized membranes, which are the outer and inner
mitochondrial membranes, creating large internal space (matrix) and much narrower space;
the intermembrane space. Both membranes are composed of a lipid bilayer membrane.
Outer membrane contains molecules of transport protein (porin), forming aqueous channels
through the lipid bilayer(permeable to ions/protons in the form of H+ and small molecules up
to 5000 Daltons).
o Inner membrane is folded into cristae, which give increased surface area for electron
transport chain proteins.
o Mitochondria originate from alpha proteobacteria according to the endosymbiotic
theory where multicellular organisms shallowed the bacteria. The bacteria became
evolved to become indispensable of the cell. Therefore the mitochondria has its own
16000 nucleotide long genome. It is only 0,5% of the whole cell genome.
- Double-stranded mtDNA has a circular structure
o Mitochondrial DNA (mtDNA): human mtDNA is a molecule of double-
stranded DNA that encodes 13 structural peptide subunits of the oxidative
phosphorylation system and 24 RNA molecules required for intra-
mitochondrial protein synthesis (22 mitochondrial tRNA and 2 mitochondrial
rRNAs).
-
