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.

真核细胞的代谢功能和能量产生由线粒体调节，线粒体被认为是真核细胞调节细胞稳态的细胞内“动力室”。线粒体功能不仅在正常发育和生理过程中很重要，而且在包括心脏病在内的各种人类病理中也很重要。心血管医学领域的一个新兴主题是线粒体核对代谢重编程的影响。这篇综述描述了线粒体类核的线性/3D 结构（例如，类核的高度组织的蛋白质-DNA 结构）以及它如何受多种因素（例如非编码 RNA 及其相关的 R 环）的调节，以用于代谢重编程心脏病。此外，我们强调了许多目前尚未解决的有关心脏代谢的问题，包括线粒体核仁的双向信号传导和细胞核中的 3D 染色质结构。特别是，我们探索了剖析线粒体核的 3D 结构的新技术，并对线粒体逆行信号传导及其如何调节线粒体疾病中的核 (3D) 染色质结构提出了新的见解。