TY - JOUR
T1 - Coordination of mitochondrial and nuclear gene-expression regulation in health, evolution, and disease
AU - Papier, Omer
AU - Minor, Gavriel
AU - Medini, Hadar
AU - Mishmar, Dan
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Mitochondrial dysfunction has been reported in monogenic phenotypes, but also as part of common complex disorders. Explanations for the underlying mechanism of both disease types mostly focused on mutations in the open-reading frames of proteins encoded by either the mitochondrial or nuclear genomes, as well as in tRNA or ribosomal RNA genes in the mitochondrial DNA (mtDNA). Although disease-causing mutations have been identified in regulatory proteins of mtDNA replication and maintenance, coordination between the regulation of mitochondrial and nuclear gene expression was only rarely considered as an explanation for mitochondrial dysfunction in diseases. Here, we review evidence suggesting that compromised coordination of mitonuclear regulation of gene expression constitutes an attractive mechanism to explain the involvement of mitochondrial dysfunction in a variety of disorders and in evolutionary processes. We discuss candidate mechanisms for coordination of mitonuclear gene expression and future avenues for their identification, with emphasis on functional genomics techniques.
AB - Mitochondrial dysfunction has been reported in monogenic phenotypes, but also as part of common complex disorders. Explanations for the underlying mechanism of both disease types mostly focused on mutations in the open-reading frames of proteins encoded by either the mitochondrial or nuclear genomes, as well as in tRNA or ribosomal RNA genes in the mitochondrial DNA (mtDNA). Although disease-causing mutations have been identified in regulatory proteins of mtDNA replication and maintenance, coordination between the regulation of mitochondrial and nuclear gene expression was only rarely considered as an explanation for mitochondrial dysfunction in diseases. Here, we review evidence suggesting that compromised coordination of mitonuclear regulation of gene expression constitutes an attractive mechanism to explain the involvement of mitochondrial dysfunction in a variety of disorders and in evolutionary processes. We discuss candidate mechanisms for coordination of mitonuclear gene expression and future avenues for their identification, with emphasis on functional genomics techniques.
UR - http://www.scopus.com/inward/record.url?scp=85132217179&partnerID=8YFLogxK
U2 - 10.1016/j.cophys.2022.100554
DO - 10.1016/j.cophys.2022.100554
M3 - Review article
AN - SCOPUS:85132217179
SN - 2468-8681
VL - 27
JO - Current Opinion in Physiology
JF - Current Opinion in Physiology
M1 - 100554
ER -