Mitochondrial nucleoid in cardiac homeostasis: bidirectional signaling of mitochondria and nucleus in cardiac diseases

Abstract

Metabolic function and energy production in eukaryotic cells are regulated by mitochondria, which have been recognized as the intracellular ‘powerhouses’ of eukaryotic cells for their regulation of cellular homeostasis. Mitochondrial function is important not only in normal developmental and physiological processes, but also in a variety of human pathologies, including cardiac diseases. An emerging topic in the field of cardiovascular medicine is the implication of mitochondrial nucleoid for metabolic reprogramming. This review describes the linear/3D architecture of the mitochondrial nucleoid (e.g., highly organized protein-DNA structure of nucleoid) and how it is regulated by a variety of factors, such as noncoding RNA and its associated R-loop, for metabolic reprogramming in cardiac diseases. In addition, we highlight many of the presently unsolved questions regarding cardiac metabolism in terms of bidirectional signaling of mitochondrial nucleoid and 3D chromatin structure in the nucleus. In particular, we explore novel techniques to dissect the 3D structure of mitochondrial nucleoid and propose new insights into the mitochondrial retrograde signaling, and how it regulates the nuclear (3D) chromatin structures in mitochondrial diseases.

The critical role of cardiolipin in metazoan differentiation, development, and maturation

“…In retrograde signaling, nuclear gene expression can be modulated in response to functional changes in downstream components of a pathway, such as changes in organelles. All but 13 mitochondrial proteins are encoded by nuclear genes (nDNA, anterograde signaling), but because mitochondria also house their own genome (mtDNA), the two genomes (nDNA and mtDNA) need to coordinate with anterograde and retrograde signaling to generate the normal mitochondrial proteome 179‐183 . Molecules and processes that have been implicated in retrograde signaling during development include ROS (see above), HIF, and the mitochondrial unfolded protein response.…”

The Roles of CircRNAs in Mitochondria

“…Human mtDNAs are packaged into nucleoids. Nucleoids are chromosome-like organellar nuclei 17 , that exhibit a discrete macromolecular assembly that determines mitochondrial genetics and dysfunction 18 and cardiac homeostasis 19 .…”

Diagnosis of acute myocardial infarction using a combination of circulating circular RNA cZNF292 and clinical information based on machine learning

“…Cardiovascular disease (CVD) is a leading threat to human lives, causing great morbidity and mortality worldwide 1,2 . Accurate and early diagnoses combined with appropriate therapeutic strategy would significantly reduce mortality and improve prognosis 3,4 .…”

“…Cardiovascular disease (CVD) is a leading threat to human lives, causing great morbidity and mortality worldwide. 1 , 2 Accurate and early diagnoses combined with appropriate therapeutic strategy would significantly reduce mortality and improve prognosis. 3 , 4 Clinical diagnosis of acute myocardial infarction (AMI) is based on electrocardiography combined with cardiac troponins, myoglobin, and creatine kinase‐MB (CK‐MB) isoenzymes.…”