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  • OverviewJanuary 31, 2018

    0 17 668
  • MinireviewJanuary 31, 2018

    0 63 1477

    Autophagy Dysregulation and Obesity-Associated Pathologies

    Sim Namkoong, Chun-Seok Cho, Ian Semple, and Jun Hee Lee

    Mol. Cells 2018; 41(1): 3-10 https://doi.org/10.14348/molcells.2018.2213
    Abstract

    Abstract : Autophagy is one of the major degradative mechanisms that can eliminate excessive nutrients, toxic protein aggregates, damaged organelles and invading microorganisms. In response to obesity and obesity-associated lipotoxic, proteotoxic and oxidative stresses, autophagy plays an essential role in maintaining physiological homeostasis. However, obesity and its associated stress insults can often interfere with the autophagic process through various mechanisms, which result in further aggravation of obesity-related metabolic pathologies in multiple metabolic organs. Paradoxically, inhibition of autophagy, within specific contexts, indirectly produces beneficial effects that can alleviate several detrimental consequences of obesity. In this minireview, we will provide a brief discussion about our current understanding of the impact of obesity on autophagy and the role of autophagy dysregulation in modulating obesity-associated pathological outcomes.

  • MinireviewJanuary 31, 2018

    0 72 1523

    The Role of Autophagy in Systemic Metabolism and Human-Type Diabetes

    Jinyoung Kim, Yu-Mi Lim, and Myung-Shik Lee

    Mol. Cells 2018; 41(1): 11-17 https://doi.org/10.14348/molcells.2018.2228
    Abstract

    Abstract : Autophagy is critical for the maintenance of organelle function and intracellular nutrient environment. Autophagy is also involved in systemic metabolic homeostasis, and its dysregulation can lead to or accelerate the development of metabolic disorders. While the role of autophagy in the global metabolism of model organisms has been investigated mostly using site-specific genetic knockout technology, the impact of dysregulated autophagy on systemic metabolism has been unclear. Here, we review recent papers showing the role of autophagy in systemic metabolism and in the development of metabolic disorders. Also included are data suggesting the role of autophagy in human-type diabetes, which are different in several key aspects from murine models of diabetes. The results shown here support the view that autophagy modulation could be a new modality for the treatment of metabolic syndrome associated with lipid overload and human-type diabetes.

  • MinireviewJanuary 31, 2018

    0 349 6506
    Abstract

    Abstract : Mitochondrial quality control systems are essential for the maintenance of functional mitochondria. At the organelle level, they include mitochondrial biogenesis, fusion and fission, to compensate for mitochondrial function, and mitophagy, for degrading damaged mitochondria. Specifically, in mitophagy, the target mitochondria are recognized by the autophagosomes and delivered to the lysosome for degradation. In this review, we describe the mechanisms of mitophagy and the factors that play an important role in this process. In particular, we focus on the roles of mitophagy adapters and receptors in the recognition of damaged mitochondria by autophagosomes. In addition, we also address a functional association of mitophagy with mitochondrial dynamics through the interaction of mitophagy adaptor and receptor proteins with mitochondrial fusion and fission proteins.

  • MinireviewJanuary 31, 2018

    0 42 2144
    Abstract

    Abstract : The cytoplasm in mammalian cells is a battlefield between the host and invading microbes. Both the living organisms have evolved unique strategies for their survival. The host utilizes a specialized autophagy system, xenophagy, for the clearance of invading pathogens, whereas bacteria secrete proteins to defend and escape from the host xenophagy. Several molecules have been identified and their structural investigation has enabled the comprehension of these mechanisms at the molecular level. In this review, we focus on one example of host autophagy and the other of bacterial defense: the autophagy receptor, NDP52, in conjunction with the sugar receptor, galectin-8, plays a critical role in targeting the autophagy machinery against Salmonella; and the cysteine protease, RavZ secreted by Legionella pneumophila cleaves the LC3-PE on the phagophore membrane. The structure-function relationships of these two examples and the directions of future research will be discussed.

  • MinireviewJanuary 31, 2018

    0 99 1638

    Mechanisms and Physiological Roles of Mitophagy in Yeast

    Tomoyuki Fukuda, and Tomotake Kanki

    Mol. Cells 2018; 41(1): 35-44 https://doi.org/10.14348/molcells.2018.2214
    Abstract

    Abstract : Mitochondria are responsible for supplying of most of the cell’s energy via oxidative phosphorylation. However, mitochondria also can be deleterious for a cell because they are the primary source of reactive oxygen species, which are generated as a byproduct of respiration. Accumulation of mitochondrial and cellular oxidative damage leads to diverse pathologies. Thus, it is important to maintain a population of healthy and functional mitochondria for normal cellular metabolism. Eukaryotes have developed defense mechanisms to cope with aberrant mitochondria. Mitochondria autophagy (known as mitophagy) is thought to be one such process that selectively sequesters dysfunctional or excess mitochondria within double-membrane autophagosomes and carries them into lysosomes/vacuoles for degradation. The power of genetics and conservation of fundamental cellular processes among eukaryotes make yeast an excellent model for understanding the general mechanisms, regulation, and function of mitophagy. In budding yeast, a mitochondrial surface protein, Atg32, serves as a mitochondrial receptor for selective autophagy that interacts with Atg11, an adaptor protein for selective types of autophagy, and Atg8, a ubiquitin-like protein localized to the isolation membrane. Atg32 is regulated transcriptionally and post-translationally to control mitophagy. Moreover, because Atg32 is a mitophagy-specific protein, analysis of its deficient mutant enables investigation of the physiological roles of mitophagy. Here, we review recent progress in the understanding of the molecular mechanisms and functional importance of mitophagy in yeast at multiple levels.

  • MinireviewJanuary 31, 2018

    0 63 1497
    Abstract

    Abstract : Autophagy is a lysosome-dependent degradation process that is essential for maintaining cellular homeostasis. In recent years, more studies have focused on the late stages of autophagy. Our group discovered and studied the terminal step of autophagy, namely autophagic lysosome reformation (ALR). ALR is the process that regenerates functional lysosomes from autolysosomes, thus maintaining lysosome homeostasis. ALR involves clathrin-mediated membrane budding from autolysosomes, elongation of membrane tubules along microtubules with the pulling force provided by the motor protein KIF5B, proto-lysosome scission by dynamin 2, and finally maturation of proto-lysosomes to functional lysosomes. In this review, we will summarize progress in unveiling the molecular mechanisms underlying ALR and its potential pathophysiological roles.

  • MinireviewJanuary 31, 2018

    0 59 2310
    Abstract

    Abstract : Atg5 and Atg7 have long been considered as essential molecules for autophagy. However, we found that cells lacking these molecules still form autophagic vacuoles and perform autophagic protein degradation when subjected to certain stressors. During this unconventional autophagy pathway, autophagosomes appeared to be generated in a Rab9-dependent manner by the fusion of vesicles derived from the trans-Golgi and late endosomes. Therefore, mammalian autophagy can occur via at least two different pathways; the Atg5/Atg7-dependent conventional pathway and an Atg5/Atg7-independent alternative pathway.

  • MinireviewJanuary 31, 2018

    0 71 1958

    Pexophagy: Molecular Mechanisms and Implications for Health and Diseases

    Dong-Hyung Cho, Yi Sak Kim, Doo Sin Jo, Seong-Kyu Choe, and Eun-Kyeong Jo

    Mol. Cells 2018; 41(1): 55-64 https://doi.org/10.14348/molcells.2018.2245
    Abstract

    Abstract : Autophagy is an intracellular degradation pathway for large protein aggregates and damaged organelles. Recent studies have indicated that autophagy targets cargoes through a selective degradation pathway called selective autophagy. Peroxisomes are dynamic organelles that are crucial for health and development. Pexophagy is selective autophagy that targets peroxisomes and is essential for the maintenance of homeostasis of peroxisomes, which is necessary in the prevention of various peroxisome-related disorders. However, the mechanisms by which pexophagy is regulated and the key players that induce and modulate pexophagy are largely unknown. In this review, we focus on our current understanding of how pexophagy is induced and regulated, and the selective adaptors involved in mediating pexophagy. Furthermore, we discuss current findings on the roles of pexophagy in physiological and pathological responses, which provide insight into the clinical relevance of pexophagy regulation. Understanding how pexophagy interacts with various biological functions will provide fundamental insights into the function of pexophagy and facilitate the development of novel therapeutics against peroxisomal dysfunction-related diseases.

  • MinireviewJanuary 31, 2018

    0 122 2812

    Autophagy and Longevity

    Shuhei Nakamura, and Tamotsu Yoshimori

    Mol. Cells 2018; 41(1): 65-72 https://doi.org/10.14348/molcells.2018.2333
    Abstract

    Abstract : Autophagy is an evolutionally conserved cytoplasmic degradation system in which varieties of materials are sequestered by a double membrane structure, autophagosome, and delivered to the lysosomes for the degradation. Due to the wide varieties of targets, autophagic activity is essential for cellular homeostasis. Recent genetic evidence indicates that autophagy has a crucial role in the regulation of animal lifespan. Basal level of autophagic activity is elevated in many longevity paradigms and the activity is required for lifespan extension. In most cases, genes involved in autophagy and lysosomal function are induced by several transcription factors including HLH-30/TFEB, PHA-4/FOXA and MML-1/Mondo in long-lived animals. Pharmacological treatments have been shown to extend lifespan through activation of autophagy, indicating autophagy could be a potential and promising target to modulate animal lifespan. Here we summarize recent progress regarding the role of autophagy in lifespan regulation.

Mol. Cells
Nov 30, 2021 Vol.44 No.11
COVER PICTURE
3D quantitative images of the vesicular structure and the nucleolus using label free optical diffraction tomography (Kim et al., pp. 851-860).

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