Yaşlanmanın Mitokondriyal Bütünlüğünün Denetlenmesi

Yaşlanma, doku ve organ fonksiyonlarında ilerleyici gerileme ile karakterize, hastalık ve ölüm riskinde artışa neden olan doğal bir olaydır. İnsan yaşlanmasına katkıda bulunan çeşitli faktörler arasında, mitokondrial disfonksiyon en önemli etkenlerden biri olarak ortaya çıkmaktadır. Mitokondrial disfonksiyon metabolik sendrom, nörodejeneratif bozukluklar, kardiyovasküler hastalıklar ve kanser gibi yaşla ilişkili patolojilerin gelişimi ile bağlantılıdır. Mitokondri, enerji ve metabolik homeostazın düzenlenmesinde merkezi olup mitokondrial hasarı sınırlandıran ve mitokondrial bütünlüğü ve işlevi sağlamak için karmaşık bir sisteme sahiptir. Ökaryotlarda çeşitli moleküler ve hücresel yolaklar, mitokondrinin kalitesini ve bütünlüğünü kontrol etmek için etkindir. Bu yolaklar, organizmanın ömrü boyunca bu temel organelin sağlıklı bir şekilde işlevini gerçekleştirmesi ile ilgilidir. Mitokondrial fonksiyonları belirleyen mitokondrial komplekslerin yanısıra mitokontriyal DNA (mtDNA)'nın bütünlüğünün denetlenmesi ve ekspresyonunun düzenlenmesi, tekli proteinlerin yeniden şekillendirilmesi için gereklidir. Mitokondri; genomik, proteomik, organeller ve hücresel seviyelerdeki altta yatan mekanizmaların anlaşılması, mitokondrial fonksiyon bozuklukları, dejeneratif süreçler, yaşlanma ve mitokondriyanın bozulmasından kaynaklanan yaşa bağlı hastalıklar için müdahale etmenin temelidir. Kalite kontrol (Quality control: QC) sistemleri, organellerin işlev bozukluğuna yol açan dejeneratif hastalıklar ve yaşlanma gibi süreçleri engeller. Bu derlemenin konusu; bugün hala tam olarak açıklanamayan yaşlanma sürecinin aydınlatılmasına neden olan mitokandriyal düzenlemenin incelenmesidir. Mitokondrial QC'de hastalık ve yaşlanma ile ilgili yolaklar; mtDNA onarımı ve yeniden organizasyonu, okside aminoasit rejenerasyonu, ağır hasar gören proteinlerin yeniden katlanması ve parçalanması, mitofajinin tümüyle mitokondrinin bozulması ve sonunda programlanmış hücre ölümü tartışılacaktır.

Anahtar Kelimeler:

Yaşlanma, Mitokondri, Yaşlanmanın Kontrolü

Control of Mitochondrial Integrity of Aging

Aging is a natural cause of progressive decline in tissue and organ functions, leading to an increased risk of disease and death. Among the various factors contributing to human aging, mitochondrial dysfunction is emerging as one of the most important factors. Mitochondrial dysfunction is linked to the development of age-related pathologies such as metabolic syndrome, neurodegenerative disorders, cardiovascular diseases and cancer. Mitochondria are central to the regulation of energy and metabolic homeostasis and have a complex system to limit mitochondrial damage and provide mitochondrial integrity and function. Several molecular and cellular pathways in eukaryotes are involved in controlling the quality and integrity of mitochondria. These pathways are concerned with the functioning of the organism in a healthy manner throughout its life cycle. The regulation of the integrity of mitochondrial DNA (mtDNA) as well as the mitochondrial complexes that determine mitochondrial functions and the regulation of expression are necessary for the reshaping of single proteins. Mitochondria; Understanding of the underlying mechanisms in genomic, proteomic, organellar and cellular levels is the basis for intervening in age-related diseases resulting from mitochondrial dysfunctions, degenerative processes, aging and deterioration of mitochondria. Quality control (QC) systems prevent processes such as degenerative diseases and aging that cause organ dysfunction. The subject of this review; the mitochondrial regulation which causes the elucidation of the aging process, which is still not fully understood today. Pathways to disease and aging in mitochondrial QC; mtDNA repair and reorganization, regeneration of oxyde aminoacids, refolding and disruption of heavily damaged proteins, degradation of mitochondria entirely by mitofargin, and eventually programmed cell death.

Keywords:

Aging, Mitochondria, Aging Control,

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