Electron Microscopic Analysis of a Spherical Mitochondrial Structure

Wen-Xing Ding; Min Li; Joanna M. Biazik; David G. Morgan; Fengli Guo; Hong-Min Ni; Michael Goheen; Eeva-Liisa Eskelinen; Xiao-Ming Yin

doi:10.1074/jbc.M112.413674

Electron Microscopic Analysis of a Spherical Mitochondrial Structure*

From the ^‡Department of Pharmacology, Toxicology, and Therapeutics, the University of Kansas Medical Center, Kansas City, Kansas 66160,
the ^§Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202,
the ^¶Department of Biosciences, Division of Biochemistry and Biotechnology, the University of Helsinki, 00014 Helsinki, Finland,
the ^‖Cryo-Transmission Electron Microscopy Facility, Indiana University, Bloomington, Indiana 47405, and
the ^**Stowers Institute for Medical Research, Kansas City, Missouri 64110

↵1 To whom correspondence may be addressed: Dept. of Pharmacology, Toxicology, and Therapeutics, The University of Kansas Medical Center, MS 1018, 3901 Rainbow Blvd., Kansas City, KS 66160. Tel.: 913-588-9813; Fax: 913-588-7501; E-mail: wxding{at}kumc.edu.
↵2 To whom correspondence may be addressed: Dept. of Pathology and Laboratory Medicine, Indiana University School of Medicine, W. 350 11th Street, Indianapolis, IN 46202. Tel.: 317-491-6096; Fax: 317-274-1782; E-mail: xmyin{at}iupui.edu.

Background: Mitochondria are dynamic organelles with variable morphological features under different functional status.

Results: Mitochondria treated with an uncoupler presented a spherical structure with an internal lumen containing cytosolic materials as defined by serial sections and electron tomography.

Conclusion: Mitochondria were able to undergo a three-dimensional structural transformation under oxidative stress.

Significance: Mitochondrial spheroid formation represents a novel mitochondrial dynamics.

Abstract

Mitochondria undergo dynamic structural alterations to meet changing needs and to maintain homeostasis. We report here a novel mitochondrial structure. Conventional transmission electron microscopic examination of murine embryonic fibroblasts treated with carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, found that more than half of the mitochondria presented a ring-shaped or C-shaped morphology. Many of these mitochondria seemed to have engulfed various cytosolic components. Serial sections through individual mitochondria indicated that they formed a ball-like structure with an internal lumen surrounded by the membranes and containing cytosolic materials. Notably, the lumen was connected to the external cytoplasm through a small opening. Electron tomographic reconstruction of the mitochondrial spheroids demonstrated the membrane topology and confirmed the vesicular configuration of this mitochondrial structure. The outside periphery and the lumen were defined by the outer membranes, which were lined with the inner membranes. Matrix and cristae were retained but distributed unevenly with less being kept near the luminal opening. Mitochondrial spheroids seem to form in response to oxidative mitochondrial damage independently of mitophagy. The structural features of the mitochondrial spheroids thus represent a novel mitochondrial dynamics.

Footnotes

↵* This work was supported, in whole or in part, by National Institutes of Health Grants R01 AA020518-01, R21AA017421, P20 RR021940, and P20 RR016475 (to W.-X. D.) and R01CA111456 and R01CA 83817 (to X.-M. Y.).
↵ This article contains supplemental Fig. S1 and Videos 1–5.