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Review
. 2021 Dec 15;10(12):3541.
doi: 10.3390/cells10123541.

Mitophagy in Yeast: Decades of Research

Ingrid Bhatia-Kissova  1 , Nadine Camougrand  2   3
Affiliations
Review

Mitophagy in Yeast: Decades of Research

Ingrid Bhatia-Kissova et al. Cells. .

Abstract

Mitophagy, the selective degradation of mitochondria by autophagy, is one of the most important mechanisms of mitochondrial quality control, and its proper functioning is essential for cellular homeostasis. In this review, we describe the most important milestones achieved during almost 2 decades of research on yeasts, which shed light on the molecular mechanisms, regulation, and role of the Atg32 receptor in this process. We analyze the role of ROS in mitophagy and discuss the physiological roles of mitophagy in unicellular organisms, such as yeast; these roles are very different from those in mammals. Additionally, we discuss some of the different tools available for studying mitophagy.

Keywords: Atg32 protein; mitochondria; mitophagy; quality control; yeast.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pathways involved in selective removal of mitochondria in yeast. (A) Conventional mitophagy relies on receptor protein Atg32. Following the activation of mitophagy, Atg32p binds to Atg8p conjugated to phosphatidylethanolamine at PAS, and Atg11, an adaptor protein, to confer selectivity for mitophagy. (B) The mitochondria-derived compartments (MDC) pathway. This process selectively sequesters a group of mitochondrial membrane proteins, mainly carrier family proteins, into vesicles that bud from the mitochondria in a Dnm1- and Tom70/71-dependent way followed by elimination by autophagy.
Figure 2
Figure 2
Mitophagy in yeast employs different signaling pathways in a context-dependent manner. In S. cerevisiae, mitophagy can be triggered by nitrogen starvation or stationary phase of growth. In each way, cells are cultured in media with respiratory carbon source and the process requires the same key proteins, such as Atg32, Atg11, and Atg8. (A) Cells submitted to starvation are harvested in a mid-exponential growth phase, and under these conditions most mitochondria are healthy and functional. Here, the role of mitophagy is to provide new nutrients by recycling redundant organelles to ensure cell survival in adverse conditions. (B) During the stationary phase of growth, mitophagy is useful to eliminate mitochondria that have been damaged or dysfunctional to maintain cellular function and homeostasis. The fact that proteins Aup1, Atg33, and Psd2 are required for the stationary phase mitophagy, but are indispensable for mitophagy induced by starvation, and conversely, that mitochondrial Psd1p is selectively required for the removal of mitochondria in nitrogen deficiency, suggests that different signaling pathways are involved in the induction of mitophagy [68].
Figure 3
Figure 3
Regulation of receptor-involved mitophagy in yeast and mammals. Following the mitophagy induction, both yeast Atg32 and mammalian FUNDC1 receptors undergo the same type of post-translational modifications. Phosphorylation of mitophagic receptors plays a pivotal role in either promoting or inhibiting mitophagy depending on the circumstances. In reaction to hypoxia or depolarization of mitochondrial membrane potential, the mitochondrial phosphatase PGAM5 interacts with FUNDC1 and dephosphorylates the serine 13 residue. This enhances its interaction with LC3, which ultimately leads to mitophagy induction. The kinase CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy induction. In addition, the mitochondrial E3 ligase MARCH5 plays a role in regulating hypoxia-induced mitophagy by ubiquitinilating FUNDC1 and causing its degradation to limit excessive mitochondrial degradation. In yeast, during nitrogen starvation or in stationary phase, CK2 kinase phosphorylates Atg32 protein on serines 114 and 119; these modifications are essential for the initiation of mitophagy. Ubiquitination is also involved in regulation of Atg32 activity.
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