title: Computational classification of mitochondrial shapes reflects stress and redox state.
abstract: Dynamic variations in mitochondrial shape have been related to function. However, tools to automatically classify and enumerate mitochondrial shapes are lacking, as are systematic studies exploring the relationship of such shapes to mitochondrial stress. Here we show that during increased generation of mitochondrial reactive oxygen species (mtROS), mitochondria change their shape from tubular to donut or blob forms, which can be computationally quantified. Imaging of cells treated with rotenone or antimycin, showed time and dose-dependent conversion of tubular forms to donut-shaped mitochondria followed by appearance of blob forms. Time-lapse images showed reversible transitions from tubular to donut shapes and unidirectional transitions between donut and blob shapes. Blobs were the predominant sources of mtROS and appeared to be related to mitochondrial-calcium influx. Mitochondrial shape change could be prevented by either pretreatment with antioxidants like N-acetyl cysteine or inhibition of the mitochondrial calcium uniporter. This work represents a novel approach towards relating mitochondrial shape to function, through integration of cellular markers and a novel shape classification algorithm.
authors: Centre for Excellence in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors: T
authors: T
authors: Ahmad
authors: K
authors: K
authors: Aggarwal
authors: B
authors: B
authors: Pattnaik
authors: S
authors: S
authors: Mukherjee
authors: T
authors: T
authors: Sethi
authors: B K
authors: BK
authors: Tiwari
authors: M
authors: M
authors: Kumar
authors: A
authors: A
authors: Micheal
authors: U
authors: U
authors: Mabalirajan
authors: B
authors: B
authors: Ghosh
authors: S
authors: S
authors: Sinha Roy
authors: A
authors: A
authors: Agrawal
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D008928:Mitochondria / Q000145:classification* / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D012402:Rotenone; C032456:antimycin; D000968:Antimycin A; D002118:Calcium; D000111:Acetylcysteine