Mitochondrial biogenesis

Mitochondrial proteins encoded from the nuclear genome need to be targeted and transported appropriately into the mitochondria.
The processes of fusion and fission allow for mitochondrial reorganization.

Process by which cells increase mitochondrial numbers.

- Mitochondrial biogenesis

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Mitochondrion

Double-membrane-bound organelle found in most eukaryotic organisms.

Two mitochondria from mammalian lung tissue displaying their matrix and membranes as shown by electron microscopy
Simplified structure of a mitochondrion.
Cross-sectional image of cristae in a rat liver mitochondrion to demonstrate the likely 3D structure and relationship to the inner membrane
Electron transport chain in the mitochondrial intermembrane space
Transmission electron micrograph of a chondrocyte, stained for calcium, showing its nucleus (N) and mitochondria (M).
Typical mitochondrial network (green) in two human cells (HeLa cells)
Model of the yeast multimeric tethering complex, ERMES
Evolution of MROs
The circular 16,569 bp human mitochondrial genome encoding 37 genes, i.e., 28 on the H-strand and 9 on the L-strand.

Mitochondrial biogenesis is in turn temporally coordinated with these cellular processes.

PPARGC1A

Protein that in humans is encoded by the PPARGC1A gene.

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices. This protein was the first to have its structure solved by X-ray crystallography. Toward the right-center among the coils, a prosthetic group called a heme group (shown in gray) with a bound oxygen molecule (red).

PGC-1α is the master regulator of mitochondrial biogenesis.

AMP-activated protein kinase

Enzyme that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low.

AMP-activated protein kinase
Active adenosine monophosphate-activated protein kinase (AMPK, left) and inactive AMPK (right). AMPK is a protein complex composed of three subunits: α (green), β (brown), and γ (blue). When bound to adenosine monophosphate (AMP), AMPK is activated and the active loop is protected against phosphatases. When bound to adenosine triphosphate (ATP), AMPK undergoes a large conformational change wherein part of the α subunit associates weakly with the γ subunit ~100Å away, the active loop is exposed to phosphatases, and AMPK is deactivated. PDB ID: 4RER (left) and 7M74 (right)

Many biochemical adaptations of skeletal muscle that take place during a single bout of exercise or an extended duration of training, such as increased mitochondrial biogenesis and capacity, increased muscle glycogen, and an increase in enzymes which specialize in glucose uptake in cells such as GLUT4 and hexokinase II are thought to be mediated in part by AMPK when it is activated.

Pyrroloquinoline quinone

Redox cofactor and antioxidant.

Structure of the antioxidant, glutathione

It is claimed that PQQ taken as a dietary supplement may promote mitochondrial biogenesis.

Skeletal muscle

Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system that are mostly attached by tendons to bones of the skeleton.

A top-down view of skeletal muscle
3D rendering of a skeletal muscle fiber
Muscle types by fiber arrangement
Types of pennate muscle. A – unipennate; B – bipennate; C – multipennate
ATPase staining of a muscle cross section. Type II fibers are dark, due to the alkaline pH of the preparation. In this example, the size of the type II fibers is considerably less than the type I fibers due to denervation atrophy.
Structure of muscle fibre showing a sarcomere under electron microscope with schematic explanation.
Diagram of sarcoplasmic reticulum with terminal cisternae and T-tubules.
Human embryo showing somites labelled as primitive segments.
When a sarcomere contracts, the Z lines move closer together, and the I band becomes smaller. The A band stays the same width. At full contraction, the thin and thick filaments overlap.
Contraction in more detail
(a) Some ATP is stored in a resting muscle. As contraction starts, it is used up in seconds. More ATP is generated from creatine phosphate for about 15 seconds. (b) Each glucose molecule produces two ATP and two molecules of pyruvic acid, which can be used in aerobic respiration or converted to lactic acid. If oxygen is not available, pyruvic acid is converted to lactic acid, which may contribute to muscle fatigue. This occurs during strenuous exercise when high amounts of energy are needed but oxygen cannot be sufficiently delivered to muscle. (c) Aerobic respiration is the breakdown of glucose in the presence of oxygen (O2) to produce carbon dioxide, water, and ATP. Approximately 95 percent of the ATP required for resting or moderately active muscles is provided by aerobic respiration, which takes place in mitochondria.
Exercise-induced signaling pathways in skeletal muscle that determine specialized characteristics of slow- and fast-twitch muscle fibers
Jogging is one form of aerobic exercise.
In muscular dystrophy, the affected tissues become disorganized and the concentration of dystrophin (green) is greatly reduced.
Prisoner of war exhibiting muscle loss as a result of malnutrition.

Ca2+/calmodulin-dependent protein kinase activity is also upregulated by slow motor neuron activity, possibly because it amplifies the slow-type calcineurin-generated responses by promoting MEF2 transactivator functions and enhancing oxidative capacity through stimulation of mitochondrial biogenesis.

Capric acid

Saturated fatty acid, medium-chain fatty acid , and carboxylic acid.

Two-dimensional representation of the saturated fatty acid myristic acid

Capric acid may be responsible for the mitochondrial proliferation associated with the ketogenic diet, and that this may occur via PPARγ receptor agonism and its target genes involved in mitochondrial biogenesis.

Wnt signaling pathway

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors.

Crystal protein structure of Wnt8 and the cysteine-rich domain of Frizzled 8
Figure 2. Wnt binds to (activates) the receptor. Axin is removed from the "destruction complex." β-Cat moves into the nucleus, binds to a transcription factor on DNA, and activates transcription of a protein. "P" represents phosphate.
Figure 1. Wnt doesn't bind to the receptor. Axin, GSK and APC form a "destruction complex," and β-Cat is destroyed.
Canonical Wnt pathway
Noncanonical PCP pathway
Noncanonical Wnt/calcium pathway
Diagram illustrating the epithelial-mesenchymal transition
Diagram illustrating the interaction between the Wnt and insulin signaling pathways

Wnt signaling is a strong activator of mitochondrial biogenesis.

Sirtuin 2

Enzyme that in humans is encoded by the SIRT2 gene.

The enzyme glucosidase converts the sugar maltose into two glucose sugars. Active site residues in red, maltose substrate in black, and NAD cofactor in yellow.

SIRT2 mediates mitochondrial biogenesis by deacetylating PGC-1α, upregulates antioxidant enzyme expression by deacetylating FOXO3a, and thereby reduces ROS levels.

Rev-ErbA beta

Member of the Rev-Erb protein family.

Cartoon diagram of the ligand binding domain of Rev-ErbA beta (rainbow colored, N-terminus = blue, C-terminus = red) complexed with heme (space-filling model, carbon atoms = white, nitrogen = blue, oxygen = red, iron = magenta) based on the crystallographic coordinates.

Rev-Erbβ plays a role in skeletal muscle mitochondrial biogenesis.

FGF21

Protein that in mammals is encoded by the FGF21 gene.

Mechanism for FGF21-mediated regulation of metabolism

FGF21 induces mitochondrial biogenesis by activating PGC-1α.