Ferritin light chain is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the ''FTL''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Ferritin is the major protein responsible for storing intracellular iron in
prokaryote
A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Con ...
s and
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bact ...
s. It is a heteropolymer consisting of 24 subunits, heavy and light ferritin chains.
This gene has multiple
pseudogene
Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes are ...
s.
It is abnormally expressed in fetuses of both
IVF and
ICSI, which may contribute to the increase risk of birth defects in these
assisted reproductive technologies.
Function
Iron is extremely important in the development of neurons, transport through iron-sulfur clusters, the electron transport chain, and synthesis and breakdown of neurotransmitters. The function of the FTL is to act as both an iron reservoir and to remove excess iron from the body. Since iron plays a role in electron transfer, there is potential for the generation of free, highly toxic radicals which makes the role of the FTL as an iron detoxifier very significant.
The rates of iron uptake and release may be affected by changes to the components of the ferritin light chains and heavy chains.
Although the ferritin light chain unlike the ferritin heavy chain has no ferroxidase activity, the light chain may be responsible for the electron transfer across the ferritin protein cage.
Clinical significance
Oxidative stress caused by iron radicals generated in the ETC and an increase in iron levels caused by defects in the FTL gene has been known to be a cause of the onset of neurodegenerative diseases and
hyperferritinemia-cataract syndrome.
Mutations of the FTL gene cause the rare adult-onset
basal ganglia disease also known as
neuroferritinopathy.
These mutations are specifically in exon four of the FTL gene. There are two distinct toxic mechanisms that lead to neuroferritinopathy and these are abnormalities in iron metabolism and the creation of free iron radicals, resulting in oxidative stress and cell death.
Interactions
Ferritin light chain has been shown to
interact with
FTH1.
An oxygen molecule acts as the terminal electron acceptor during the oxidation of iron in aerobic metabolism. A study conducted with different apoferritins with distinct compositions of heavy and light subunits revealed that both subunits have key roles in the electron transport chain.
Neither subunit on its own has the ability to reduce
cytochrome c
The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apoptosis. Cytochrome c is hig ...
and thus the first step, the oxidation of Fe
2+ to Fe
3+, can be carried out by the heavy chain and the light chains are responsible for the transfer of electrons.
FTL is regulated by iron and with an increase in iron, there is both an increase in the FTL expression and
PEN-2 levels, which results in increased γ- secretase activity. In relation to this, the downregulation of FTL expression leads to a decrease in the protein levels of
PEN-2.
See also
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Ferritin
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Neuroferritinopathy
{{PDB Gallery, geneid=2512