Astrocytes resolve ER stress through mitochondrial fusion facilitated by biotin availability
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ORIGINAL PAPER
Astrocytes resolve ER stress through mitochondrial fusion facilitated by biotin availability Ramaian Santhaseela Anand 1 & Dhasarathan Ganesan 1 & Sudarshana Rajasekaran 1 & Tamilselvan Jayavelu 1 Received: 29 April 2020 / Revised: 7 June 2020 / Accepted: 10 June 2020 # Cell Stress Society International 2020
Abstract Structures of cellular organelles are intertwined with their functions that undergo alterations once the organelles are stressed. Since organelle functions are dependent on each other, an organelle-specific stress possibly influences the structure and function of its associated organelles. In this perspective, our study demonstrated that endoplasmic reticulum (ER)-specific stress induced by tunicamycin in primary astroglial culture is associated with altered mitochondrial dynamics and matched with the changes as observed in the aging rat brain. However, the exogenous addition of biotin, a highly lipogenic and mitochondrial vitamin, ameliorates ER stress even though its direct targets are not known within ER. Alternatively, the increased biotinylation of mitochondrial carboxylases preserves its basal respiratory capacity by upregulating mitofusin 2 (Mfn2) and, possibly, its associated role on mitochondrial fusion. Furthermore, the Mfn2 increase by biotin augments physical interaction between ER and functional mitochondria to exchange biomolecules as a part of ER stress resolution. This suggests an increased demand for micronutrient biotin under ER stress resolves the same by undergoing appropriate structural and metabolic contacts between ER and mitochondria. These findings provide a paradigm to resolve stress in one organelle by sustaining the metabolic commitments of another interdependent organelle. The findings also highlight a novel role of biotin in inducing Mfn2 expression and localization under ER stress in addition to its known role as a co-enzyme. Keywords ER stress . Biotin . Mitochondrial dynamics . Mitochondrial respiration
Introduction Cells display specialized structural changes within their organelles to favor their basal function and stress adaptations. Alterations in the execution of these structural changes result in disease pathology. For example, an imbalance in the regulation of mitochondrial structural dynamics is associated with a wide range of age-related pathologies such as Parkinson’s disease and Alzheimer’s disease (Reddy 2014). Mitochondrial morphology is shaped by ongoing events of fusion and fission of the outer and inner mitochondrial membranes. Uncontrolled fission is known to cause mitochondrial fragmentation and leads to
Anand Ramaian Santhaseela and Dhasarathan Ganesan contributed equally to this work. * Tamilselvan Jayavelu [email protected]; [email protected] 1
Centre for Biotechnology, Anna University, Chennai 600025, India
metabolic dysfunction and disease. Uncontrolled fusion is known to result in a hyper fused network to counteract metabolic insults, preservation of cellular integrity, and escape from autophagic clearance (Wai and La
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