Mitochondrial Gene Expression and Beyond—Novel Aspects of Cellular Physiology

Abstract

Mitochondria are peculiar organelles whose proper function depends on the crosstalk between two genomes, mitochondrial and nuclear. The human mitochondrial genome (mtDNA) encodes only 13 proteins; nevertheless, its proper expression is essential for cellular homeostasis, as mtDNA-encoded proteins are constituents of mitochondrial respiratory complexes. In addition, mtDNA expression results in the production of RNA molecules, which influence cell physiology once released from the mitochondria into the cytoplasm. As a result, dysfunctions of mtDNA expression may lead to pathologies in humans. Here, we review the mechanisms of mitochondrial gene expression with a focus on recent findings in the field. We summarize the complex turnover of mitochondrial transcripts and present an increasing body of evidence indicating new functions of mitochondrial transcripts. We discuss mitochondrial gene regulation in different cellular contexts, focusing on stress conditions. Finally, we highlight the importance of emerging aspects of mitochondrial gene regulation in human health and disease.

PolG Inhibits Glycolysis by Suppressing PKM2 Phosphorylation Resulting Reduced Gastric Cancer Proliferation

“…In previous studies, it was shown that PolG is a mitochondrial DNA polymerase, which plays an important role in maintaining the stability of mitochondrial DNA. The abnormality of PolG could directly affect the function of the respiratory chain which is composed of proteins synthesized by transcription of mitochondrial DNA and downstream signal modulation of cellular metabolism [19][20][21]. It has also been reported that PolG promotes metabolic reprogramming in various types of tumor cells by affecting mitochondrial function in tumor cells [11][12][13].…”

The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System

“…The mitochondrial gene expression has been recently reviewed by Kotrys et al Transcription initiation sites are located within the D-loop region of both heavy chain (H, rich in guanine) and light chain (L, rich in cytosine). H chain is a template for the transcription of the majority of mitochondrial genes [90]. Transcription of the L chain results mostly in non-coding RNAs, which are degraded by mitochondrial degradosome (a complex of polynucleotide phosphorylase (PNPT1) and ATP-dependent RNA helicase (SUV3).…”

“…On the other hand, new factors are described as engaged in the transcription e.g., mitochondrial ribosomal protein L7/L12 (MRPL12) or mitochondrial transcription rescue factor 1 (MTRES1), which is also involved in translation through binding to the mitochondrial ribosome. New findings indicate that mitochondrial gene expression processes are yet to be fully understood [90]. Translation in mitochondria consists of standard stages of initiation, elongation, termination, and recycling.…”

“…The free 3′-OH end formed this way allows DNA polymerase γ (Polγ) to add the missing nucleotide. Polγ is still commonly accepted as the only one (from 17) mammalian polymerase reported functioning in mitochondria, despite recent advances in the field [ 90 , 154 ]. BER in mitochondria resembles the one in the nucleus.…”

Identification of a Novel Variant in EARS2 Associated with a Severe Clinical Phenotype Expands the Clinical Spectrum of LTBL

“…Mitochondrial diseases are a group of clinically heterogeneous disorders caused by dysfunction of the oxidative phosphorylation (OXPHOS) system and can arise due to defects in genes in the nuclear or mitochondrial DNA (nDNA and mtDNA, respectively) [ 1 ]. Human mtDNA contains 37 genes encoding 13 subunits of the OXPHOS complexes I, III, IV, and V and two ribosomal RNAs (rRNA) and 22 transfer RNAs (tRNAs) crucial for their translation [ 2 ]. The remaining components of mtDNA replication, transcription, and translation processes, including tRNA maturation, initiation and elongation factors, ribosomal proteins, and aminoacyl-tRNA synthetases (mt-aaRSs), are encoded by nDNA, synthesized in the cytosol, and imported into the mitochondria [ 3 , 4 ].…”