Mitochondrial Biomarkers in the Omics Era: A Clinical-Pathophysiological Perspective

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 May 11

PMID 38732076

Authors

Jacopo Gervasoni

Aniello Primiano

Michela Cicchinelli

Lavinia Santucci

Serenella Servidei

Andrea Urbani

Guido Primiano

Federica Iavarone

Affiliations

Soon will be listed here.

Abstract

Mitochondrial diseases (MDs) affect 4300 individuals, with different ages of presentation and manifestation in any organ. How defects in mitochondria can cause such a diverse range of human diseases remains poorly understood. In recent years, several published research articles regarding the metabolic and protein profiles of these neurogenetic disorders have helped shed light on the pathogenetic mechanisms. By investigating different pathways in MDs, often with the aim of identifying disease biomarkers, it is possible to identify molecular processes underlying the disease. In this perspective, omics technologies such as proteomics and metabolomics considered in this review, can support unresolved mitochondrial questions, helping to improve outcomes for patients.

References

DiMauro S, Schon E, Carelli V, Hirano M . The clinical maze of mitochondrial neurology. Nat Rev Neurol. 2013; 9(8):429-44. PMC: 3959773. DOI: 10.1038/nrneurol.2013.126. View

Rahman S . Mitochondrial disease in children. J Intern Med. 2020; 287(6):609-633. DOI: 10.1111/joim.13054. View

Gervasoni J, Primiano A, Marini F, Sabino A, Biancolillo A, Calvani R . Fourier-Transform Infrared Spectroscopy of Skeletal Muscle Tissue: Expanding Biomarkers in Primary Mitochondrial Myopathies. Genes (Basel). 2020; 11(12). PMC: 7766922. DOI: 10.3390/genes11121522. View

Luft R, IKKOS D, Palmieri G, Ernster L, AFZELIUS B . A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control: a correlated clinical, biochemical, and morphological study. J Clin Invest. 1962; 41:1776-804. PMC: 291101. DOI: 10.1172/JCI104637. View

Shaham O, Slate N, Goldberger O, Xu Q, Ramanathan A, Souza A . A plasma signature of human mitochondrial disease revealed through metabolic profiling of spent media from cultured muscle cells. Proc Natl Acad Sci U S A. 2010; 107(4):1571-5. PMC: 2824369. DOI: 10.1073/pnas.0906039107. View

Tragni V, Primiano G, Tummolo A, Cafferati Beltrame L, La Piana G, Sgobba M . Personalized Medicine in Mitochondrial Health and Disease: Molecular Basis of Therapeutic Approaches Based on Nutritional Supplements and Their Analogs. Molecules. 2022; 27(11). PMC: 9182050. DOI: 10.3390/molecules27113494. View

Pickett S, Grady J, Ng Y, Gorman G, Schaefer A, Wilson I . Phenotypic heterogeneity in m.3243A>G mitochondrial disease: The role of nuclear factors. Ann Clin Transl Neurol. 2018; 5(3):333-345. PMC: 5846390. DOI: 10.1002/acn3.532. View

Spinelli J, Haigis M . The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018; 20(7):745-754. PMC: 6541229. DOI: 10.1038/s41556-018-0124-1. View

Chen R, Snyder M . Promise of personalized omics to precision medicine. Wiley Interdiscip Rev Syst Biol Med. 2012; 5(1):73-82. PMC: 4154620. DOI: 10.1002/wsbm.1198. View

10.

Alix J, Plesia M, Lloyd G, Dudgeon A, Kendall C, Hewamadduma C . Rapid identification of human muscle disease with fibre optic Raman spectroscopy. Analyst. 2022; 147(11):2533-2540. PMC: 9150427. DOI: 10.1039/d1an01932e. View

11.

Lu H, Wang X, Li M, Ji D, Liang D, Liang C . Mitochondrial Unfolded Protein Response and Integrated Stress Response as Promising Therapeutic Targets for Mitochondrial Diseases. Cells. 2023; 12(1). PMC: 9818186. DOI: 10.3390/cells12010020. View

12.

Esterhuizen K, Lindeque J, Mason S, van der Westhuizen F, Rodenburg R, de Laat P . One mutation, three phenotypes: novel metabolic insights on MELAS, MIDD and myopathy caused by the m.3243A > G mutation. Metabolomics. 2021; 17(1):10. DOI: 10.1007/s11306-020-01769-w. View

13.

Suomalainen A, Battersby B . Mitochondrial diseases: the contribution of organelle stress responses to pathology. Nat Rev Mol Cell Biol. 2017; 19(2):77-92. DOI: 10.1038/nrm.2017.66. View

14.

Delaney N, Sharma R, Tadvalkar L, Clish C, Haller R, Mootha V . Metabolic profiles of exercise in patients with McArdle disease or mitochondrial myopathy. Proc Natl Acad Sci U S A. 2017; 114(31):8402-8407. PMC: 5547614. DOI: 10.1073/pnas.1703338114. View

15.

Southwell N, Primiano G, Nadkarni V, Attarwala N, Beattie E, Miller D . A coordinated multiorgan metabolic response contributes to human mitochondrial myopathy. EMBO Mol Med. 2023; 15(7):e16951. PMC: 10331581. DOI: 10.15252/emmm.202216951. View

16.

Hall A, Vilasi A, Garcia-Perez I, Lapsley M, Alston C, Pitceathly R . The urinary proteome and metabonome differ from normal in adults with mitochondrial disease. Kidney Int. 2014; 87(3):610-22. DOI: 10.1038/ki.2014.297. View

17.

DiMauro S . Mitochondrial encephalomyopathies--fifty years on: the Robert Wartenberg Lecture. Neurology. 2013; 81(3):281-91. PMC: 3959764. DOI: 10.1212/WNL.0b013e31829bfe89. View

18.

Gorman G, Schaefer A, Ng Y, Gomez N, Blakely E, Alston C . Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015; 77(5):753-9. PMC: 4737121. DOI: 10.1002/ana.24362. View

19.

Schon K, Ratnaike T, van den Ameele J, Horvath R, Chinnery P . Mitochondrial Diseases: A Diagnostic Revolution. Trends Genet. 2020; 36(9):702-717. DOI: 10.1016/j.tig.2020.06.009. View

20.

Ruiz M, Cuillerier A, Daneault C, Deschenes S, Frayne I, Bouchard B . Lipidomics unveils lipid dyshomeostasis and low circulating plasmalogens as biomarkers in a monogenic mitochondrial disorder. JCI Insight. 2019; 4(14). PMC: 6675547. DOI: 10.1172/jci.insight.123231. View