Since high-throughput omics technologies have in recent years been highly efficacious tools in mitochondrial research, we searched the PubMed, Google Scholar, and Web of Science databases to identify original research using omics technologies that has led to exciting developments in mitochondrial biology and disease. Search terms included the different subtypes of omics (“genomics”, “transcriptomics”, “proteomics”, “metabolomics”, etc.) combined with “mitochondrial”. In addition, terms such as
ReviewMitochondrial medicine in the omics era
Section snippets
Mitochondrial function and dysfunction
Mitochondria are complex dynamic organelles that execute myriad functions pertaining to cellular metabolism and homoeostasis. Cellular energy generation via oxidative phosphorylation (OXPHOS) is a hallmark of mitochondria, but mitochondria also play roles in calcium homoeostasis, initiation of caspase-dependent apoptosis, cellular stress response, haem biosynthesis, sulphur metabolism, and cytosolic protein degradation.1, 2 A unique feature of mitochondria is the mitochondrial DNA (mtDNA), a
Enhanced understanding of oxidative phosphorylation
Perhaps the most well characterised function of the mitochondrion and the rationale behind its alternative name as the so-called powerhouse of the cell is cellular energy generation via OXPHOS. The OXPHOS system, which is conserved from bacteria to higher eukaryotes, comprises five multimeric enzymes, named complexes I to V, and two mobile electron carriers (coenzyme Q10 [CoQ10], and cytochrome c [cyt c]).7 Complex I (NADH:ubiquinone oxidoreductase [CI]) pumps four protons across the inner
Mitochondria as signalling organelles and gatekeepers of cellular homoeostasis
An emerging concept in mitochondrial biology is the role of mitochondria as signalling organelles in constant communication with the nucleus and other subcellular compartments to titrate energy production and metabolites to the cell's specific needs and nutrient availability.22 Omics studies have revealed details about retrograde signals from the mitochondrion to the cytosol, which include ROS, the mitochondrial membrane potential, key intermediary metabolites, mitochondrial bioenergetic
Genomics
The initial era of mitochondrial genomics began 30 years ago with the discovery of sporadic large-scale mtDNA rearrangements in patients with ragged-red fibre myopathies and of maternally inherited mtDNA point mutations in families with Leber hereditary optic neuropathy (LHON).36, 37 The small size and known sequence38 of the mitochondrial genome led to a plethora of reports of novel disease-associated mutations, spanning almost every base of the mtDNA.39, 40 During this period it became
New mitochondrial disease mechanisms
Mechanisms underpinning mitochondrial disease pathology are poorly understood. However, in recent years, use of omics technologies to elucidate novel pathophysiological mitochondrial mechanisms has led to exciting and often unexpected developments. Bioenergetic deficit due to ineffective OXPHOS is a starting point for explaining the pathophysiology of mitochondrial disease, and can be especially true for patients with mutations affecting OXPHOS components. However, failure to detect ATP
Translational medicine
The promise of omics means that it is now more important than ever to become trial ready for mitochondrial diseases. However, many challenges continue to impede the development of effective therapies for mitochondrial disease. A major hindrance has been the extreme clinical heterogeneity of affected patients, even within genetically homogeneous groups caused by the same recessive defect. It is very unlikely that a single therapy will reverse all the phenotypic manifestations of a mitochondrial
Conclusions
The mitochondrion is a complex organelle where many pathways and cell functions overlap. Furthermore, critical crosstalk with other subcellular organelles contributes to the remarkable complexity and heterogeneity of mitochondrial disorders. Recent advances in multifaceted omics technologies have, and will continue to, disentangle enigmatic features of mitochondrial disease, revolutionise the field of mitochondrial medicine, and hopefully pave the way for the development of effective therapies
Search strategy and selection criteria
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Targeting of CRISPR-Cas12a crRNAs into human mitochondria
2024, BiochimieKnockdown of BRAWNIN minimally affect mitochondrial complex III assembly in human cells
2024, Biochimica et Biophysica Acta - Molecular Cell ResearchRecent advances in neurometabolic diseases: The genetic role in the modern era
2023, Epilepsy and BehaviorProtein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases
2024, Hepatology Communications