Korean Circ J.  2020 May;50(5):395-405. 10.4070/kcj.2019.0416.

Mitochondrial Quality Control in the Heart: New Drug Targets for Cardiovascular Disease

• Oh CM
• Ryu D
• Cho S
• Jang Y

• KMID: 2471778
• DOI: http://doi.org/10.4070/kcj.2019.0416

Abstract

Despite considerable efforts to prevent and treat cardiovascular disease (CVD), it has become the leading cause of death worldwide. Cardiac mitochondria are crucial cell organelles responsible for creating energy-rich ATP and mitochondrial dysfunction is the root cause for developing heart failure. Therefore, maintenance of mitochondrial quality control (MQC) is an essential process for cardiovascular homeostasis and cardiac health. In this review, we describe the major mechanisms of MQC system, such as mitochondrial unfolded protein response and mitophagy. Moreover, we describe the results of MQC failure in cardiac mitochondria. Furthermore, we discuss the prospects of 2 drug candidates, urolithin A and spermidine, for restoring mitochondrial homeostasis to treat CVD.

Keyword

Mitochondrial quality control; Heart; Urolithin A; Spermidine

MeSH Terms

Adenosine Triphosphate
Cardiovascular Diseases*
Cause of Death
Heart Failure
Heart*
Homeostasis
Mitochondria
Mitochondrial Degradation
Organelles
Quality Control*
Spermidine
Unfolded Protein Response
Adenosine Triphosphate
Spermidine

Figure

• 

  Figure 1 Mitochondrial quality control system. Under normal condition, ATFS-1 and PINK1 proteins goes into mitochondria and are degraded. After mitochondrial stress, disrupted mitochondrial integrity and function induces mitochondrial stress responses for restoring mitochondrial and cellular homeostasis. ATFS-1 traffics to the nucleus and activates transcriptional responses to recover mitochondrial function. Damaged mitochondria are marked by PINK1 and removed by mitophagy pathway.ATFS = activating transcription factor associated with stress; FGF = fibroblast growth factor; GDF = growth differentiation factor; PINK1 = PTEN-induced kinase 1; Ub = ubiquitin; ROS = reactive oxygen species.

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