‘Mitochondria are the powerhouses of the cell’ is a well-known fact that every child learns in middle school. Mitochondria use a process called oxidative phosphorylation (OXPHOS) to produce adenosine triphosphate (ATP), the primary source of energy for most cellular activity. Genes contained within the mitochondria’s own genetic material (mtDNA) are vital for OXPHOS.
Different cells have different energy requirements. Heart muscle cells, or cardiomyocytes, are always active and require a steady supply of large amounts of energy. “Under normal conditions, cardiomyocytes derive more than 90% of their ATP from mitochondrial OXPHOS, and mitochondria occupy up to 40% of the cell volume in adult cardiac cells ,” says Professor Tao P. Zhong from the School of Life Sciences at East China Normal University, China.
OXPHOS is a vital cellular process that requires careful management. Many reactive oxygen species (ROS) are released during the process, which could harm other cellular components. In addition, cardiomyocytes need to carefully regulate the production of new mitochondria and the destruction of defective mitochondria, respectively called biogenesis and mitophagy. These processes—biogenesis, mitochondrial dynamics, and mitophagy—are managed by a multi-tiered system called mitochondrial quality control (MQC). Disruptions of the MQC and mitochondrial dysfunction are seen in patients with heart failure, severe diabetes, hypertension, and ischemia-reperfusion (I/R) injuries after a heart attack.
In a review paper published on April 5, 2026, in Volume 139 of the Chinese Medical Journal , Prof. Zhong and his collaborators have described the molecules that constitute the MQC, as well as epigenetic and transcriptional controls over mitochondrial function. Understanding these factors could guide the development of innovative treatments for cardiac disorders.
The core of MQC is a highly conserved sequence of proteins. At its center is Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). PGC-1α increases or slows mitochondrial biogenesis based on the cardiomyocyte’s internal and external environment. PGC-1α interacts with nuclear respiratory factors (NRFs), estrogen related receptors (ERRs) and peroxisome-proliferator activated receptors (PPARs) to drive biogenesis and increase or decrease the rate of ATP production.
NRFs and ERRs affect the replication of mtDNA and the activation of mitochondrial genes. PPARs regulate the balance between glucose and fatty acid metabolism depending on energy availability.
The activation and suppression of PGC-1α and other proteins in the MQC depend on a number of transcription factors that are produced in response to the cellular environment. DNA methylation of both MQC genes and mtDNA is used to regulate mitochondrial activity and mitophagy.
Different cardiac disorders disrupt mitochondrial activity in different ways. I/R injuries cause great oxidative stress, mitochondrial overload, and cell death. Heart Failure and hypertension reduce PGC-1 activity, and cardiomyocytes have too few mitochondria to function properly. Diabetes patients have altered mitophagy in their cardiomyocytes.
“ Emerging therapeutic strategies are increasingly focused on the precise molecular components of mitochondria ,” says Dr. Ping Zhu from Southern Medical University, China. Modulating mitochondrial biogenesis and enhancing mitophagy may help to reduce oxidative stress after I/R injuries. Increasing fatty acid metabolism reduces heart failure linked to obesity. Antioxidants such as Coenzyme Q10 and vitamin C, specifically targeted at mitochondria, help reduce oxidative stress and dysfunction. However, the relative success of these therapies depends on the cellular microenvironment. Severely damaged mitochondria may not respond properly, or worse, deteriorate more quickly to these drugs.
All things considered, Prof. Zhong is optimistic about the future of mitochondria-targeted therapies. He believes that a multiomics approach that looks at the network effects of various proteins will help us understand the complex interactions responsible for the many kinds of mitochondrial dysfunction. These approaches will also reveal new molecular targets for therapies.
“ Moving forward, research should prioritize the development of real-time monitoring techniques, the validation of MQC-modulating agents in clinical settings, and the integration of systems-level approaches to elucidate the nuanced interplay between mitochondrial homeostasis and pathological processes. These efforts will ultimately pave the way for innovative treatments aimed at preserving mitochondrial and cardiac function under pathological stress, ” concludes Prof. Zhong.
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Reference
DOI: 10.1097/CM9.0000000000004011
About East China Normal University
Founded in 1951, East China Normal University (ECNU) is one of China’s most prestigious universities. Its 207 hectares of campus area in Shanghai houses over 35,000 students and 4,400 faculty members. The university also hosts three National Key Laboratories and a host of other national research facilities. International collaborations with distinguished universities in Europe, North America, Asia and Australia give ECNU a global outlook. Times Higher Education places ECNU in the top 300 universities globally and 56 th in Asia.
URL: https://english.ecnu.edu.cn/
About Southern Medical University
Southern Medical University is a leading public medical institution in Guangzhou, China, founded in 1951 as the First Military Medical University of the People’s Liberation Army. It became a national key university in 1979 and was renamed in 2004 after transitioning to civilian administration. The university is jointly supported by China’s Ministry of Education, National Health Commission, and Guangdong Province. With multiple schools, affiliated hospitals, and strong research programs, it offers undergraduate to doctoral education. Known for excellence in clinical medicine and international collaboration, it ranks among China’s top medical universities and attracts students worldwide.
URL: https://www.smu.edu.cn/english/
About Professor Tao P. Zhong from East China Normal University
Dr. Tao P. Zhong is a Professor at the School of Life Sciences, East China Normal University. His research focuses on the cellular and molecular mechanisms regulating cardiovascular development and organ morphogenesis, using Zebrafish and mammalian stem cells as models. Prof. Zhong has over 60 research articles to his credit. He has been named ‘Outstanding Young Scientist of China’ by the National Natural Science Foundation of China.
About Dr. Ping Zhu from Southern Medical University
Dr. Ping Zhu is a medical researcher affiliated with Southern Medical University, Guangzhou. Her work focuses on endocrinology, metabolism, and chronic diseases, including diabetes and cardiovascular conditions. She has contributed to peer-reviewed research aimed at improving patient outcomes through evidence-based approaches. With a strong background in clinical and translational research, Dr. Zhu continues to advance understanding of disease mechanisms and public health challenges.
Chinese Medical Journal
Literature review
Cells
Regulation of mitochondrial biogenesis and energy metabolism in the heart
5-Apr-2026
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