Mitochondrial biology and dysfunction in secondary mitochondrial disease

Abstract

Mitochondrial diseases are a broad, genetically heterogeneous class of metabolic disorders characterized by deficits in oxidative phosphorylation (OXPHOS). Primary mitochondrial disease (PMD) defines pathologies resulting from mutation of mitochondrial DNA (mtDNA) or nuclear genes affecting either mtDNA expression or the biogenesis and function of the respiratory chain. Secondary mitochondrial disease (SMD) arises due to mutation of nuclear-encoded genes independent of, or indirectly influencing OXPHOS assembly and operation. Despite instances of novel SMD increasing year-on-year, PMD is much more widely discussed in the literature. Indeed, since the implementation of next generation sequencing (NGS) techniques in 2010, many novel mitochondrial disease genes have been identified, approximately half of which are linked to SMD. This review will consolidate existing knowledge of SMDs and outline discrete categories within which to better understand the diversity of SMD phenotypes. By providing context to the biochemical and molecular pathways perturbed in SMD, we hope to further demonstrate the intricacies of SMD pathologies outside of their indirect contribution to mitochondrial energy generation.

Research Progress on Chinese Medicine Regulation of Mitochondrial Damage for Intervention in Respiratory System Diseases

“…Mitochondria affects oxidative stress and immune responses by regulating calcium signals and their homeostasis, participating in cell differentiation, signal transduction, and apoptosis. 1 Mitochondrial damage refers to abnormal changes in mitochondrial structure and function, including large-scale loss of mitochondrial DNA, and changes in membrane structure, electron transfer function through the respiratory chain, mitochondrial transmembrane potential difference, etc., 2,3 resulting in mitochondrial oxidative stress, mitochondrial autophagy, mitochondrial DNA mutations, telomere shortening, etc. A large number of studies have confirmed that mitochondrial damage plays an important role in the occurrence and development of respiratory system diseases.…”

Mitochondrial Neurodegenerative Diseases: Three Mitochondrial Ribosomal Proteins as Intermediate Stage in the Pathway That Associates Damaged Genes with Alzheimer’s and Parkinson’s

“…Generally, the term "mitochondrial disease" describes a heterogeneous set of conditions caused by genetic defects in the assembly and/or function of OXPHOS proteins [45]. In fact, mitochondria play a fundamental role in energy production and are essential in numerous cellular processes [35,46]. Consequently, mitochondrial dysfunction often propagates and/or underlies many pathological states, including neurodegenerative diseases [47,48] and the aging process [49,50].…”

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“…However, the term "mitochondrial diseases" has recently been broadened to include another set of pathologies, called secondary mitochondrial dysfunctions, caused by mutations in nuclear genes not related to the OXPHOS assembly and activity. They affect diverse mitochondrial functions including, among others, protein biogenesis, mitochondrial morphology and dynamics, lipid biogenesis, and the Krebs cycle (Ceccatelli Berti et al, 2021;Baker et al, 2022). iMD diagnosis remains a challenge given their clinical, biochemical, and molecular heterogeneities.…”