ophthalmologyОфтальмологияOphthalmology in Russia1816-50952500-0845Ophthalmology10.18008/1816-5095-2021-3S-646-653ophthalmology-1635Research ArticleСтатьиРоль митофагии при наследственных оптических нейропатиях. Обзор литературыThe Role of Mitophagy in Hereditary Optic Neuropathies. Literature Reviewhttps://orcid.org/0000-0001-7329-5725АндрееваН. А.AndreevaN. A.

Андреева Наталья Алексеевна, кандидат медицинских наук, научный сотрудник отделения патологии сетчатки и зрительного нерва 

ул. Россолимо, 11а, б, Москва, 119021

Andreeva Nataliya A., PhD, researcher of Retinal and Optic Nerve Pathology Department 

Rossolimo str., 11A, B, Moscow, 119021

natalia.hanakova@gmail.comhttps://orcid.org/0000-0003-4597-4987ШереметН. Л.SheremetN. L.

Шеремет Наталия Леонидовна, доктор медицинских наук, главный научный сотрудник отделения патологии сетчатки и зрительного нерва 

ул. Россолимо, 11а, б, Москва, 119021

Sheremet Nataliya L., MD, chief researcher of Retinal and Optic Nerve Pathology Department 

Rossolimo str., 11A, B, Moscow, 119021

https://orcid.org/0000-0002-1251-6405МураховскаяЮ. К.MurakhovskayaYu. K.

Мураховская Юлия Константиновна, клинический ординатор 

ул. Россолимо, 11а, б, Москва, 119021

Murakhovskaya Iulia K., resident

Rossolimo str., 11A, B, Moscow, 119021

ДаялА. А.DayalA. A.

Даял Александр Абдулаевич, инженер-исследователь 

ул. Вавилова, 34, Москва, 119334

Dayal Alexander A., research engineer 

Vavilova str., 34, Moscow, 119334

МининА. А.MininA. A.

Минин Александр Александрович, ведущий научный сотрудник, кандидат биологических наук, заведующий отделом клеточной биологии 

ул. Вавилова, 34, Москва, 119334

Minin Alexander A., candidate of biological sciences, leading researcher, head of the Cell Biology Department 

Vavilova str., 34, Moscow, 119334

ФГБНУ «Научно-исследовательский институт глазных болезней»РоссияResearch Institute of Eye DiseasesRussian FederationФГБУН «Институт белка» Российской академии наукРоссияInstitute of Protein Research of Russian Academy of SciencesRussian Federation202119102021183S646653Copyright © Андреева Н.А., Шеремет Н.Л., Мураховская Ю.К., Даял А.А., Минин А.А., 20212021Андреева Н.А., Шеремет Н.Л., Мураховская Ю.К., Даял А.А., Минин А.А.Andreeva N.A., Sheremet N.L., Murakhovskaya Y.K., Dayal A.A., Minin A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.ophthalmojournal.com/opht/article/view/1635

В обзоре литературы рассматривается роль митофагии при наследственных оптических нейропатиях. Митохондрии, внутриклеточные двухмембранные органеллы, одни из основных компонентов всех эукариотических клеток, выполняют множество различных функций в клетке. Однако основная функция митохондрий — снабжение клеток энергией в форме АТФ. Синтез АТФ осуществляется благодаря работе пяти белковых комплексов дыхательной цепи, основные компоненты которой располагаются на внутренней мембране митохондрий. Известно, что белки, образующие все комплексы дыхательной цепи (кроме II), кодируются и ядерными, и митохондриальными генами. Нарушения в работе электрон-транспортной цепи митохондрий приводят к развитию митохондриальных заболеваний, которые могут возникать в результате мутаций как в мтДНК, так и в яДНК. Наиболее распространенными митохондриальными заболеваниями органов зрения являются наследственные оптические нейропатии (НОН), такие как наследственная оптическая нейропатия Лебера (НОНЛ). Основной причиной, приводящей к заболеванию, являются мутации генов митохондриальных белков, приводящие к нарушению работы комплексов дыхательной цепи (преимущественно I), что в результате приводит к повреждению митохондрий. Для своевременного удаления поврежденных митохондрий в клетках имеются специальные регуляторные системы, ответственные за обнаружение, изоляцию и деградацию этих органелл при помощи специфической формы аутофагии, митофагии. Для нормального функционирования клеткам необходимо поддерживать постоянный баланс между биогенезом митохондрий и процессами митофагии, нарушение этого баланса приводит к развитию заболеваний. Было выявлено, что при НОНЛ нарушена митофагия, которая является важным механизмом защиты ганглиозных клеток сетчатки. Таким образом, активация митофагии у таких пациентов может иметь определенное терапевтическое значение. Представлен обзор некоторых фармакологических препаратов, таких как рапамицин, трегалоза, метформин, спермидин, NAD+ , способных индуцировать митофагию и тем самым замедлять развитие патологического процесса у больных наследственными оптическими нейропатиями, в частности НОНЛ.

The role of mitophagy in hereditary optic neuropathies is considering in this review. Mitochondria are intracellular double membrane organelles. They are one of the main components of all eukaryotic cells, they perform many different functions in the cell. However, the main function of mitochondria is to supply cells with energy in the form of ATP. The ATP synthesis is carried out due to the respiratory chain five protein complexes work, the main components of the chain are located in the inner mitochondrial membrane. It is known that proteins that form all respiratory chain complexes (except II) are encoded by both nuclear and mitochondrial genes. The mitochondrial electron transport chain dysfunction leads to the mitochondrial diseases development, which can be a result of mutations both in mtDNA and in nDNA. The most common eye mitochondrial diseases are hereditary optic neuropathies (HON), such as Leber Hereditary Optic Neuropathy (LHON). The main cause leading to the disease are mtDNA mutations. These mutations lead to the respiratory chain complexes dysfunction (mainly I), which results in mitochondrial damage. To remove damaged mitochondria in time, cells have special regulatory systems. These systems are responsible for the damaged mitochondria detection, isolation and degradation through a specific form of autophagy, mitophagy. For normal functioning, cells need to maintain a constant balance between mitochondrial biogenesis and mitophagy. A violation of this balance leads to the disease. It was revealed that mitophagy, an important retinal ganglion cells protection mechanism, is impaired in patients with LHON. The mitophagy activation may have the therapeutic potential. Some pharmacological agents activate mitophagy and thereby slow down the disease development in patients with hereditary optic neuropathies, such as LHON. Some of them, such as rapamycin, trehalose, metformin, spermidine, NAD+ , are described in the review.

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The authors declare that there are no conflicts of interest present.