The emerging role of mitochondria as signaling organelles raises the question of whether individual mitochondria can initiate heterotypic communication with neighboring organelles. Using fluorescent probes targeted to the endoplasmic-reticulum-mitochondrial interface, we demonstrate that single mitochondria generate oxidative bursts, rapid redox oscillations, confined to the nanoscale environment of the interorganellar contact sites. Using probes fused to inositol 1,4,5-trisphosphate receptors (IP₃Rs), we show that Ca²⁺ channels directly sense oxidative bursts and respond with Ca²⁺ transients adjacent to active mitochondria. Application of specific mitochondrial stressors or apoptotic stimuli dramatically increases the frequency and amplitude of the oxidative bursts by enhancing transient permeability transition pore openings. Conversely, blocking interface Ca²⁺ transport via elimination of IP₃Rs or mitochondrial calcium uniporter channels suppresses ER-mitochondrial Ca²⁺ feedback and cell death. Thus, single mitochondria initiate local retrograde signaling by miniature oxidative bursts and, upon metabolic or apoptotic stress, may also amplify signals to the rest of the cell.

线粒体作为信号细胞器的新兴作用提出了一个问题，即单个线粒体是否可以启动与邻近细胞器的异型通讯。使用靶向内质-网-线粒体界面的荧光探针，我们证明单个线粒体产生氧化爆发、快速氧化还原振荡，仅限于细胞器间接触位点的纳米级环境。使用与肌醇 1,4,5-三磷酸受体 (IP ₃ Rs) 融合的探针，我们发现 Ca ²⁺通道直接感知氧化爆发并响应 Ca ²⁺与活跃的线粒体相邻的瞬变。特定线粒体应激物或凋亡刺激的应用通过增强瞬时渗透性过渡孔开口显着增加了氧化爆发的频率和幅度。相反，通过消除 IP _{3 Rs 或线粒体钙单向转运通道阻断界面 Ca} ²⁺转运可抑制 ER-线粒体 Ca ²⁺反馈和细胞死亡。因此，单个线粒体通过微型氧化爆发启动局部逆行信号传导，并且在代谢或凋亡应激下，也可能将信号放大到细胞的其余部分。