Metabolic control of mitophagy

Abstract

Mitochondrial dysfunction is a major hallmark of ageing and related chronic disorders. Controlled removal of damaged mitochondria by the autophagic machinery, a process known as mitophagy, is vital for mitochondrial homeostasis and cell survival. The central role of mitochondria in cellular metabolism places mitochondrial removal at the interface of key metabolic pathways affecting the biosynthesis or catabolism of acetyl‐coenzyme A, nicotinamide adenine dinucleotide, polyamines, as well as fatty acids and amino acids. Molecular switches that integrate the metabolic status of the cell, like AMP‐dependent protein kinase, protein kinase A, mechanistic target of rapamycin and sirtuins, have also emerged as important regulators of mitophagy. In this review, we discuss how metabolic regulation intersects with mitophagy. We place special emphasis on the metabolic regulatory circuits that may be therapeutically targeted to delay ageing and mitochondria‐associated chronic diseases. Moreover, we identify outstanding knowledge gaps, such as the ill‐defined distinction between basal and damage‐induced mitophagy, which must be resolved to boost progress in this area.

Emodin: an alveolar macrophage protector in acute pancreatitis induced lung injury

“…The results showed that a decrease of mitochondria level was observed at 2h after caerulein-induced acute pancreatitis mouse model, and a continuous reduction till 24h after the event. It has been demonstrated that mitochondrial plays a critical role in regulating inflammatory responses through its genuine DAMPs which serve as physical scaffold for activating pattern recognition receptors (PRRs) 9 . Specifically, mitochondria provide a distinctive framework for DAMP redistribution, PRR signaling, and inflammation responded to cellular stress; on the other hand, these processes could stimulate innate and adaptive immune reactions to maintain the homeostasis 10 .…”

“…Selective autophagy of mitochondria, known as mitophagy, is critical for eliminating damaged mitochondria 7 and preserving the integrity of the mitochondrial network 8 . Because the energic production in mitochondrial is mainly oxygen-dependence, the capacity of mitochondrial of generating ATP will be significantly impacted under such conditions, sequentially leading to cellular dysfunction 9 . Then, dysfunctional mitochondria triggers the severe inflammatory responses which exacerbate lung injury and multi-organ failure 10 .…”

Decoding HiPSC-CM’s Response to SARS-CoV-2: mapping the molecular landscape of cardiac injury

“…An inadequate amount of ATP is produced when fatty acid metabolism, glucose metabolism, and mitochondrial function are impaired [ 32 ]. Normal cellular biological activities, including gene transcription, DNA replication, and protein translation, as well as many aspects of protein modification, such as ubiquitination and acetylation, and cellular and mitochondrial autophagic processes, are affected [ 33 , 34 ]. Biological processes such as these are dependent upon the mitochondria's functionality and are critical to maintaining cell health.…”