Mitokondrinin İşlevsel Rolleri

Year 2025, Volume: 8 Issue: 3, 1478 - 1487, 16.06.2025

İlknur Güç

https://doi.org/10.47495/okufbed.1550868

Abstract

Mitokondri, ATP üretimi, kalsiyum homeostazisi, hücre proliferasyonu, programlanmış hücre ölümü ve amino asitlerin, nükleotidlerin ve lipitlerin sentezi dahil olmak üzere çeşitli hücresel metabolik süreçlerde rol oynar. Her mitokondrinin kendi genomu olmasına rağmen çoğu mitokondriyal protein nükleer DNA tarafından kodlanır. Çoğu ökaryotik hücrede bulunan hücre altı organelleri olan mitokondri, trikarboksilik asit döngüsü (TCA döngüsü),oksidatif fosforilasyon (OXPHOS), amino asit metabolizması ve yağ asidi oksidasyonu dahil olmak üzere çok sayıda metabolik ağ işleminden sorumludur. Bunlar arasında mitokondrinin en önemli fizyolojik işlevi besinleri oksitleyerek ATP üretmektir. Adenozin 5′-trifosfat (ATP) üretimine katılmak için mitokondri, serbest radikallerin üretildiği bu metabolik ağ işlemleriyle etkileşime giren karmaşık bir sistem kullanır. Genel olarak, mitokondriyal reaktif oksijen türleri (ROS) üretimi esas olarak mitokondriyal iç membran üzerinde yer alan elektron taşıma zinciri bölgesinde meydana gelir ve elektronların kompleks I ve kompleks III'ten sızması oksijen tüketimine ve süperoksit oluşumuna yol açar. Mitokondriyal redoks homeostazisi, mitokondriyal fonksiyonun ve hücre kaderinin belirlenmesinin temelini oluşturan ROS üretimi ve süpürme arasındaki dengeyi ifade eder. Bu derleme, mitokondrinin işlevsel rollerini özetlemektedir.

Keywords

ATP , Mitokondri , Mitokondriyal işlev , ROS , TCA döngüsü

Functional Roles of Mitochondria

Abstract

Mitochondria play a role in various cellular metabolic processes, including ATP production, calcium homeostasis, cell proliferation, programmed cell death, and the synthesis of amino acids, nucleotides, and lipids. Although each mitochondrion has its own genome, most mitochondrial proteins are encoded by nuclear DNA. Mitochondria, which are subcellular organelles found in most eukaryotic cells, are responsible for numerous metabolic network processes, including the tricarboxylic acid cycle (TCA cycle), oxidative phosphorylation (OXPHOS), amino acid metabolism, and fatty acid oxidation. Among these, the most important physiological function of mitochondria is to produce ATP by oxidizing nutrients. To participate in the production of adenosine 5′-triphosphate (ATP), mitochondria use a complex system that interacts with these metabolic network processes, where free radicals are produced. In general, mitochondrial reactive oxygen species (ROS) production occurs mainly at the electron transport chain site located on the mitochondrial inner membrane, and leakage of electrons from complex I and complex III leads to oxygen consumption and superoxide formation. Mitochondrial redox homeostasis refers to the balance between ROS production and scavenging that underlies mitochondrial function and cell fate determination. This review summarizes functional roles of mitochondria.

Keywords

ATP , Mitochondria , Mitochondrial function , ROS , TCA cycle

References

• Ahlqvist KJ., Hamalainen RH., Yatsuga S., Uutela M., Terzioğlu M., Götz A., Forsström S., Salven P., Angers-Loustau A., Kopra OH., Tyynismaa H., Larsson NG., Wartiovaara K., Prolla T., Trifunovic A., Suomalainen A. Somatic progenitor cell vulnerability to mitochondrial DNA mutagenesis underlies progeroid phenotypes in polg mutator mice. Cell Metabolism 2012; 15(1): 100–109.
• Anderson NM., Mucka P., Kern JG., Feng H. The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell 2018; 9(2): 216–237.
• Annesley SJ., Fisher PR. Mitochondria in health and disease. Cells 2019; 8(7): 680.
• Arany Z., Foo SY., Ma Y., Ruas JL., Bommi-Reddy A., Girnun G., Cooper M., Laznik D., Chinsomboon J., Rangwala SM., Baek KH., Rosenzweig A., Spiegelman BM. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1 alpha. Nature 2008; 451: 1008–1012.
• Arnold I., Langer T. Membrane protein degradation by AAA proteases in mitochondria. Biochimica et Biophysica Acta 2002; 1592(1): 89-96.
• Azzam EI., Jay-Guerin JP., Pain D. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Letters 2012; 327(1-2): 48–60.
• Bode M., Longen S., Morgan B., Peleh V., Dick TB., Bihlmaier K., Herrmann JM. Inaccurately assembled cytochrome c oxidase can lead to oxidative stress-induced growth arrest. Antioxid Redox Signal 2013; 18(13): 1597–612.
• Casanova A.,Wevers A., Navarro-Ledesma S., Pruimboom L. Mitochondria: It is all about energy. Frontiers in Physiology 2023; 14: 1114231.
• Cunniff B., McKenzie AJ., Heintz NH., Howe AK. AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion. Molecular Biology of The Cell 2016; 27(17): 2662–2674.
• Diaz F., Kotarsky H., Fellman V., Moraes CT. Mitochondrial disorders caused by mutations in respiratory chain assembly factors. Semiars in Fetal and Neonatal Medicine 2011; 16(4): 197–204.
• Efremov RG., Sazanov LA. Respiratory complex I: ‘steam engine’ of the cell. Current Opinion in Structural Biology 2011; 21(4): 532–540.
• Friedmann JR., Lackner LL., West M., DiBenedetto JR., Nunnari J., Voeltz GK. ER tubules mark sites of mitochondrial division. Science 2011; 334(6054): 358–362.
• Glynn SE. Multifunctional mitochondrial AAA proteases. Frontiers in Molecular Biosciences 2017; 4: 34.
• Hamanaka RB, Chandel NS. Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends in Biochemical Sciences 2010; 35(9): 505–513.
• Hoppeler H., Fluck M. Plasticity of skeletal muscle mitochondria: structure and function. Medicine and Science in Sports and Exercise 2003; 35(1): 95–104.
• Jager S., Handschin C., St-Pierre J., Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1 alpha. Proceedings of The National Academy of Sciences of the United States of America 2007; 104(29): 12017–12022.
• Jeninga EH., Schoonjans K., Auwerx J. Reversible acetylation of PGC-1: connecting energy sensors and effectors to guarantee metabolic flexibility. Oncogene 2010; 29: 4617–4624.
• Khalimonchuk O., Bird A., Winge DR. Evidence for a pro-oxidant intermediate in the assembly of cytochrome oxidase. The Journal of Biological Chemistry 2007; 282(24): 17442–17449.
• Krylatov AV., Maslov LN., Voronkov NS., Boshchenko AA., Popov SV., Gomez L., Wang H., Jaggi AS., Downey JM. Reactive oxygen species as intracellular signaling molecules in the cardiovascular system. Current Cardiology Reviews 2018; 14(4): 290-300.
• Lackner LL. Shaping the dynamic mitochondrial network. BMC Biology 2014; 12: 35.
• Lewis SC., Uchiyama LF., Nunnari J. ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells. Science 2016; 353(6296).
• Martinez-Reyes I., Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nature Communications 2020; 11: 102.
• Mihaylova MM., Shaw RJ. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nature Cell Biology 2011; 13: 1016–1023.
• Murley A., Lackner LL., Osman C., West M., Voeltz GK.,Walter P., Nunnari J. ER-associated mitochondrial division links the distribution of mitochondria and mitochondrial DNA in yeast. Elife 2013; 14: 2.
• Murphy MP. How mitochondria produce reactive oxygen species. The Biochemical Journal 2009; 417(1): 1–13.
• O’Neill LA., Kishton RJ., Rathmell J. A guide to immunometabolism for immunologists. Nature Reviews Immunology 2016; 16: 553-565.
• Onishi M., Okamoto K. Mitochondrial clearance: mechanisms and roles in cellular fitness. FEBS Letters 2021; 595: 1239–1263.
• Opalinska M., Janska H. AAA proteases: guardians of mitochondrial function and homeostasis. Cells 2018; 7(10): 163.
• Ray PD., Huang BW., Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 2012; 24(5): 981–990.
• Starkov AA.The role of mitochondria in reactive oxygen species metabolism and signaling.Annals of the New York Academy of Sciences 2008, 1147: 37-52.
• Walker BR., Moraes CT. Nuclear-mitochondrial interactions. Biomolecules 2022; 12(3): 427.
• Zhao H., Pan X. Mitochondrial Ca2+ and cell cycle regulation. International Review of Cell and Molecular Biology 2021; 362: 171–207.