Control of Mitochondrial Integrity of Aging

Year 2018, , 680 - 705, 15.04.2018

Yusuf Döğüş , Mehmet Akif Çürük

https://doi.org/10.30569/adiyamansaglik.396221

Abstract

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

Yaşlanmanın Mitokondriyal Bütünlüğünün Denetlenmesi

Abstract

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.

Keywords

Yaşlanma, Mitokondri, Yaşlanmanın Kontrolü

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