Mitochondria are interesting structures within cells.
First, we get our mitochondria only from our mother, not father.
Maternal Inheritance of Mitochondrial DNA
Second, mitochondria have a separate set of genes that are different than those found in cell nucleus.
Moreover, proteins present in a mitochondrion can be encoded by both mitochondrial located genes and nucleus located genes.
Last but not least, mitochondria are often called the power house of cells. They produce ATP, an energy currency, to meet the energy requirement of an organism. The respiratory chain in a mitochondrion is important in producing ATP. Five protein complexes (complex I, complex II, complex III, complex IV and complex V) are involved in the process of oxidative phosphorylation, which eventually produce ATP.
Abnormalities of mitochondria in skeletal muscle are found in about 50% of individuals with Leigh syndrome. The abnormalities are diverse, and many different components in mitochondria can be affected . The gene mutations related to Leigh syndrome affect proteins in complex I, II, IV or V, or can disturb the assembly of these complexes . Therefore, the activities of these complexes are disrupted or reduced, ultimately leading to Leigh syndrome.
Cellular Respiration (Respiratory Chain of Mitochondria)
Complex I (NADH dehydrogenase) deficiency, complex II (succinate dehydrogenase, which is not shown in the video) deficiency, complex III (cytochrome bc1 complex), complex IV (cytochrome oxidase) deficiency, and complex V (ATP synthase) deficiency can all contribute to Leigh syndrome.
Complex I passes electrons from NADH to ubiquinone while pumping hydrogen ions out of the mitochondrial matrix into the space between the two membranes. It has 35 nuclear-encoded subunits and 7 mitochondrial-encoded subunits. Consequently, Leigh Syndrome with mutations in the nuclear-encoded subunits shows an autosomal recessive inheritance pattern while Leigh syndrome with mutations in the mitochondrial-encoded subunits shows a maternal inheritance pattern .
Complex II is involved in the Krebs cycle, converting succinate to fumerate and passing electrons to the ubiquinone in the respiratory chain. All four subunits of complex II are encoded by nuclear DNA, and the Leigh syndrome with Complex II deficiency has an autosomal recessive inheritance .
Complex III transfers electrons from succinate and nicotinamide adenine dinucleotide-linked dehydrogenases to cytochrome c. The protein underlying Complex III deficiency facilitates the assembly of complex III. It is encoded by BCS1L gene on chromosome 2, and the associated Leigh syndrome is relatively rare  . The observed cases suggest an autosomal recessive inheritance.
The most common cause of Leigh syndrome is mutations in complex IV (also called cytochrome c oxidase or COX). Complex IV transfers electrons from cytochrome c to oxygen. It has 10 nuclear-encoded subunits and 3 mitochondrial-encoded subunits. Although autosomal recessive inheritance is more common for COX deficiency, no mutation has been found in the 10 nuclear-encoded subunits. In fact, the underlying genetic defects are unknown in the majority of the patients .
The gene most frequently mutated in COX-deficient Leigh syndrome is SURF1, which is found in nuclear DNA and contributes to the assembly of the COX complex. In cellular respiration, the COX complex provides energy for the next step that would generate ATP. Mutations in the SURF1 gene lead to the production of abnormal SURF1 proteins that would reduce the formation of COX complexes, thus impairing mitochondrial ATP production .
The French Canadian type of Leigh Syndrome (LSFC) is associated with COX deficiency, which is particularly severe in the liver . LRPPRC gene variation(s) underlies LSFC, and LSFC is inherited in an autosomal recessive mode.
Subunit 6 of Complex V (aka. ATP synthase) is encoded by mitochondrial DNA and its defects can contribute to Leigh syndrome. Consequently, the related Leigh syndrome shows a maternal mode of inheritance. The most common mutation is on the 8993th amino acid, a change from threonine to glycine .
Mutations in genes encoding mitochondrial tRNA proteins were found in a few patients and associated with myoclonus epilepsy and ragged red fibers (MERRF) .
Coenzyme Q10 deficiency is also associated with Leigh syndrome .