Mitochondrial DNA-related disorders: emphasis on mechanisms and heterogeneity

Mitochondrial diseases are a heterogeneous group of disorders that are currently the focus of intense research. The many cell functions performed by mitochondria include ATP production, calcium homeostasis, and apoptosis. One of the unique properties of mitochondria is the existence of a separate mitochondrial genome (mitochondrial DNA, mtDNA) found in varying copy numbers and containing 37 genes, 13 of them encoding proteins. All 13 mitochondrially encoded proteins form part of oxidative phosphorylation complexes through combination with approximately 100 nuclear DNA-encoded proteins. Coregulation of nDNA and mtDNA is therefore essential for mitochondrial function, and this coregulation contributes to the heterogeneity and complexity observed in mitochondrial disorders. In recent times, significant advances have been made in our understanding of mtDNA-related disorders. A comprehensive review of these studies will benefit both current and new researchers and clinicians involved in the field. This review examines the major types of mtDNA-related defects and their pathogenic mechanisms, with a special emphasis on the heterogeneity of mitochondrial disorders. Potential treatment strategies specialized for each of the disorders, including the hormone melatonin and the recent advances in gene therapy, related to their potential applications for the management of the primary mtDNA disorders are also discussed.

Mitochondrial DNA-related disorders: emphasis on mechanisms and heterogeneity

Mitochondrial diseases are a heterogeneous group of disorders that are currently the focus of intense research. The many cell functions performed by mitochondria include ATP production, calcium homeostasis, and apoptosis. One of the unique properties of mitochondria is the existence of a separate mitochondrial genome (mitochondrial DNA, mtDNA) found in varying copy numbers and containing 37 genes, 13 of them encoding proteins. All 13 mitochondrially encoded proteins form part of oxidative phosphorylation complexes through combination with approximately 100 nuclear DNA-encoded proteins. Coregulation of nDNA and mtDNA is therefore essential for mitochondrial function, and this coregulation contributes to the heterogeneity and complexity observed in mitochondrial disorders. In recent times, significant advances have been made in our understanding of mtDNA-related disorders. A comprehensive review of these studies will benefit both current and new researchers and clinicians involved in the field. This review examines the major types of mtDNA-related defects and their pathogenic mechanisms, with a special emphasis on the heterogeneity of mitochondrial disorders. Potential treatment strategies specialized for each of the disorders, including the hormone melatonin and the recent advances in gene therapy, related to their potential applications for the management of the primary mtDNA disorders are also discussed.

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Turkish Journal of Biology-Cover
  • ISSN: 1300-0152
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

DNA protective and antioxidative effects of melatonin in streptozotocin-induced diabetic rats

Selim SEKKİN, Eda Duygu İPEK, Murat BOYACIOĞLU, Cavit KUM, Ümit KARADEMİR, Hande Sultan YALINKILINÇ, Mehmet Onur AK, Hulki BAŞALOĞLU

Prooxidant effects of melatonin: a brief review

Malwina S MUNIK, Cem EKMEKÇİOĞLU

Melatonin is a potent modulator of antioxidative defense and cellular proliferation against aluminum toxicity in rats

Nihal Ömür BULAN, Guner SARIKAYA-UNAL, Sevim TUNALI, Pelin Arda PİRİNÇÇİ, Refiye YANARDAG

The effects of agomelatine and melatonin on ECoG activity of absenceepilepsy model in WAG/Rij rats

Hatice AYGÜN, Duygu AYDIN, Sema İNANIR, Fatih EKİCİ, Mustafa AYYILDIZ, Erdal AĞAR

Effects of photoperiod variations and alpha-lipoic acid treatment on melatonin,cortisol, and oxidative stress levels in the blood of rats

Cahide ÇEVİK, Recep ASLAN

The effects of topical melatonin on oxidative stress, apoptosis signals,and p53 protein expression during cutaneous wound healing

Azize ŞENER, Özge ÇEVİK, Özge DOĞAN, Nazli Gül ALTINDİŞ, Halil AKSOY, Betül OKUYAN

Mitochondrial DNA-related disorders: emphasis on mechanisms and heterogeneity

Umut CAGIN, Jose Antonio ENRIQUEZ

Melatonin, mitochondria, and Ca2+ homeostasis in the exocrine pancreas: an overview

Antonio GONZALEZ, Patricia SANTOFIMIA-CASTAÃ'O, Gines Maria SALIDO

The effects of midazolam and etomidate on the antioxidant system in the rat liver

Dilek BAYRAM, Meral ÖNCÜ, Efkan UZ, Haci Ramazan YILMAZ, Ayşe YİĞİT, Ahmet KOÇAK

Melatonin attenuates apoptosis and mitochondrial depolarization levels in hypoxic conditions of SH-SY5Y neuronal cells induced by cobalt chloride (CoCl2)

Abdülhadi Cihangir UĞUZ, Abdülhadi Cihangir UĞUZ, Ahmi ÖZ, Ahmi ÖZ, Büşra YILMAZ, Seda ALTUNBAŞ, Ömer ÇELİK