Mitochondrially encoded tRNA isoleucine also known as MT-TI is a

transfer RNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

which in humans is encoded by the

mitochondrial A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

''MT-TI''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Structure

The ''MT-TI'' gene is located on the p arm of the

mitochondrial DNA Mitochondrial DNA (mtDNA and mDNA) is the DNA located in the mitochondrion, mitochondria organelles in a eukaryotic cell that converts chemical energy from food into adenosine triphosphate (ATP). Mitochondrial DNA is a small portion of the D ...

at position 12 and it spans 69 base pairs. The structure of a

tRNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed

clover Clovers, also called trefoils, are plants of the genus ''Trifolium'' (), consisting of about 300 species of flowering plants in the legume family Fabaceae originating in Europe. The genus has a cosmopolitan distribution with the highest diversit ...

Function

MT-TI is a small 69 nucleotide

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

(human mitochondrial map position 4263-4331) that transfers the amino acid

isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...

to a growing

polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...

chain at the

ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...

site of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

synthesis during

translation Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...

Clinical significance

Mutations in ''MT-TI'' can result in multiple mitochondrial deficiencies and associated disorders.

Myoclonic epilepsy with ragged-red fibers (MERRF)

Mutations in the ''MT-TI'' gene have been associated with myoclonic epilepsy with ragged-red fibers (MERRF). Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and

nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...

. In most cases, the signs and symptoms of this disorder appear during childhood or

adolescence Adolescence () is a transitional stage of human Developmental biology, physical and psychological Human development (biology), development that generally occurs during the period from puberty to adulthood (typically corresponding to the age o ...

. The features of MERRF vary widely among affected individuals, even among members of the same family. Common symptoms include,

myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle, a joint, or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus ( myo- "muscle", clonus "spasm") describes a medical sign and, ...

myopathy In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. ''Myopathy'' means muscle disease ( Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meaning implies that the primary defec ...

spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...

dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), malnutrition, poor nourishment, poor circulatory system, circulation, loss of hormone, ...

, and more.

Cardiomyopathy

Mutations in the ''MT-TI'' gene may also cause

cardiomyopathy Cardiomyopathy is a group of primary diseases of the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...

, a disorder of the

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

characterized by the thickening of the heart, usually in the

interventricular septum The interventricular septum (IVS, or ventricular septum, or during development septum inferius) is the stout wall separating the ventricle (heart), ventricles, the lower chambers of the heart, from one another. The interventricular septum is di ...

, which results in a weakened heart muscle that is unable to pump blood effectively. It is unclear why such mutations result in the symptoms of isolated cardiomyopathy. Mutations of 4300A>G, 4295A>G, 4269A>G, and 4317A>G in the ''MT-TI'' gene have been found in patients with cardiomyopathy in varying severities and onset.

Complex IV Deficiency

''MT-TI'' mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the

cytochrome c oxidase The enzyme cytochrome c oxidase or Complex IV (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and the mitochondria of eukaryotes. It is the last enzyme in the Cellular respir ...

deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including

skeletal muscles Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

, the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

, or the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

. Common clinical manifestations include

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but it is a potential manifestation of many different dis ...

, and encephalomyopathy,

lactic acidosis Lactic acidosis refers to the process leading to the production of lactate by anaerobic metabolism. It increases hydrogen ion concentration tending to the state of acidemia or low pH. The result can be detected with high levels of lactate and lo ...

, and

hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which muscle tissues of the heart become thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ...

. A patient with a 4269A>G mutation in ''MT-TI'' was found with the deficiency.