Abstract
Mitochondria generate the energy to sustain cell viability and serve as a hub for cell signalling. Their own genome (mtDNA) encodes genes critical for oxidative phosphorylation. Mutations of mtDNA cause major disease and disability with a wide range of presentations and severity. We review here an emerging body of data suggesting that changes in cell metabolism and signalling pathways in response to the presence of mtDNA mutations play a key role in shaping disease presentation and progression. Understanding the impact of mtDNA mutations on cellular energy homeostasis and signalling pathways seems fundamental to identify novel therapeutic interventions with the potential to improve the prognosis for patients with primary mitochondrial disease.
Highlights
Mitochondria generate the energy to sustain cell viability and serve as a hub for cell signalling
We focus on how mutations of mitochondrial DNA (mtDNA) interact with cell signalling pathways, influencing mitochondrial quality control mechanisms and shaping the presentation and progression of the associated primary mitochondrial diseases
Concluding remarks Primary mitochondrial diseases are a heterogeneous group of diseases that can manifest at any age, affect almost any tissue, and vary radically in clinical presentation and severity
Summary
Subunit peptides of OxPhos, translated from genes encoded either in nDNA or mtDNA, assemble in the mitochondrial inner membrane and perform respiratory function, during which electrons from NADH and FADH2, generated mainly by the tricarboxylic acid (TCA) cycle, are transferred along a series of four multi-polypeptide respiratory complexes [1,2,3,4,5,9] This oxygen-dependent process is coupled with the generation of the mitochondrial membrane potential (ΔΨm) by actively pumping protons from the mitochondrial matrix into the intermembrane space, providing the energy that drives the synthesis of ATP by the F1Fo-ATP synthase. We focus on how mutations of mtDNA interact with cell signalling pathways, influencing mitochondrial quality control mechanisms and shaping the presentation and progression of the associated primary mitochondrial diseases.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
